title: A Phase I/II study evaluating escalating doses of recombinant human albumin-interferon-alpha fusion protein in chronic hepatitis C patients who have failed previous interferon-alpha-based therapy.
abstract: Albumin-interferon-alpha (IFN-alpha) is a novel 85.7-kDa recombinant protein consisting of IFN-alpha that is genetically fused to human serum albumin. In this Phase I/II, multicentre, open-label study, we evaluated the safety and tolerability, pharmacokinetics and pharmacodynamics of albumin-IFN-alpha in IFN-alpha-experienced patients with chronic hepatitis C. Albumin-IFN-alpha was administered in 22 escalating doses (7-900 microg) in a single injection or in two injections 14 days apart. In the 119 patients studied, there were no discontinuations because of adverse events, and albumin-IFN-alpha had a favourable safety profile at doses up to 900 microg. The most common adverse events were headache (56%), fatigue (52%), injection site erythema (38%), arthralgias (32%) and pyrexia (27%). Reduced clearance resulted in a mean elimination half-life of 159 h, which supports dosing at 2- to 4-week intervals. Induction of the IFN-specific gene OAS1 was maintained for > or = 28 days following a single injection of albumin-IFN-alpha at doses of > or = 40 microg. Dose-dependent antiviral activity was observed in this IFN-alpha-experienced study population. Antiviral activity of > or = 1.0-log reductions in HCV RNA was observed in 47% (37/78) of patients in the 120- to 900-microg cohorts and in 59% (16/27) in the 400- to 900-microg double-injection cohorts. These results support further clinical studies of albumin-IFN-alpha for the treatment of patients with chronic hepatitis C.
authors.affiliation: Mayo Clinic, Phoenix, AZ, USA. Balan.Vijayan@mayo.edu
authors.forename: Vijayan
authors.initials: V
authors.lastname: Balan
authors.forename: David R
authors.initials: DR
authors.lastname: Nelson
authors.forename: Mark S
authors.initials: MS
authors.lastname: Sulkowski
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Everson
authors.forename: Louis R
authors.initials: LR
authors.lastname: Lambiase
authors.forename: Rusell H
authors.initials: RH
authors.lastname: Wiesner
authors.forename: Rolland C
authors.initials: RC
authors.lastname: Dickson
authors.forename: Anthony B
authors.initials: AB
authors.lastname: Post
authors.forename: Robert R
authors.initials: RR
authors.lastname: Redfield
authors.forename: Gary L
authors.initials: GL
authors.lastname: Davis
authors.forename: Avidan U
authors.initials: AU
authors.lastname: Neumann
authors.forename: Blaire L
authors.initials: BL
authors.lastname: Osborn
authors.forename: William W
authors.initials: WW
authors.lastname: Freimuth
authors.forename: G Mani
authors.initials: GM
authors.lastname: Subramanian
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D012709:Serum Albumin / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000075462:Serum Albumin, Human; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D012709:Serum Albumin; C473631:albuferon; D000075462:Serum Albumin, Human