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

• Published in: Antiviral therapy Vol. 11; no. 1; pp. 35 - 45
• Main Authors: Balan, Vijayan, Nelson, David R, Sulkowski, Mark S, Everson, Gregory T, Lambiase, Louis R, Wiesner, Rusell H, Dickson, Rolland C, Post, Anthony B, Redfield, Robert R, Davis, Gary L, Neumann, Avidan U, Osborn, Blaire L, Freimuth, William W, Subramanian, G Mani
• Format: Journal Article
• Language: English
• Published: England 2006
• Subjects: Adult; Aged; Antiviral Agents - administration & dosage; Antiviral Agents - adverse effects; Antiviral Agents - pharmacokinetics; Antiviral Agents - therapeutic use; Dose-Response Relationship, Drug; Female; Hepatitis C, Chronic - drug therapy; Hepatitis C, Chronic - virology; Humans; Interferon-alpha - administration & dosage; Interferon-alpha - adverse effects; Interferon-alpha - pharmacokinetics; Interferon-alpha - therapeutic use; Male; Middle Aged; Serum Albumin - administration & dosage; Serum Albumin - adverse effects; Serum Albumin - pharmacokinetics; Serum Albumin - therapeutic use; Serum Albumin, Human; Treatment Outcome
• ISSN: 1359-6535; 2040-2058
• DOI: 10.1177/135965350601100111

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.