A Phase I/II study evaluating escalating doses of recombinant human albumin-interferon-α fusion protein in chronic hepatitis C patients who have failed previous interferon-α-based therapy

Vijayan Balan, David R. Nelson, Mark S. Sulkowski, Gregory T. Everson, Louis Lambiase, Rusell H. Wiesner, Rolland C. Dickson, Anthony B. Post, Robert R. Redfield, Gary L. Davis, Avidan U. Neumann, Blaire L. Osborn, William W. Freimuth, G. Mani Subramanian

Research output: Contribution to journalArticle

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Abstract

Albumin-interferon-α (IFN-α) is a novel 85.7-kDa recombinant protein consisting of IFN-α 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-α in IFN-α-experienced patients with chronic hepatitis C. Albumin-IFN-α was administered in 22 escalating doses (7-900 μg) 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-α had a favourable safety profile at doses up to 900 μg. 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 ≥28 days following a single injection of albumin-IFN-α at doses of ≥40 μg. Dose-dependent antiviral activity was observed in this IFN-α-experienced study population. Antiviral activity of ≥1.0-log reductions in HCV RNA was observed in 47% (37/78) of patients in the 120- to 900-μg cohorts and in 59% (16/27) in the 400- to 900-μg double-injection cohorts. These results support further clinical studies of albumin-IFN-α for the treatment of patients with chronic hepatitis C.

Original languageEnglish (US)
Pages (from-to)35-45
Number of pages11
JournalAntiviral Therapy
Volume11
Issue number1
StatePublished - Mar 6 2006
Externally publishedYes

Fingerprint

Chronic Hepatitis C
Interferons
Injections
Proteins
Antiviral Agents
Therapeutics
Safety
Arthralgia
Erythema
Recombinant Proteins
Serum Albumin
Fatigue
Headache
Half-Life
albumin interferon
Fever
Pharmacokinetics
RNA
Population
Genes

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

A Phase I/II study evaluating escalating doses of recombinant human albumin-interferon-α fusion protein in chronic hepatitis C patients who have failed previous interferon-α-based therapy. / Balan, Vijayan; Nelson, David R.; Sulkowski, Mark S.; Everson, Gregory T.; Lambiase, Louis; 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.

In: Antiviral Therapy, Vol. 11, No. 1, 06.03.2006, p. 35-45.

Research output: Contribution to journalArticle

Balan, V, Nelson, DR, Sulkowski, MS, Everson, GT, Lambiase, L, Wiesner, RH, Dickson, RC, Post, AB, Redfield, RR, Davis, GL, Neumann, AU, Osborn, BL, Freimuth, WW & Subramanian, GM 2006, 'A Phase I/II study evaluating escalating doses of recombinant human albumin-interferon-α fusion protein in chronic hepatitis C patients who have failed previous interferon-α-based therapy', Antiviral Therapy, vol. 11, no. 1, pp. 35-45.
Balan, Vijayan ; Nelson, David R. ; Sulkowski, Mark S. ; Everson, Gregory T. ; Lambiase, Louis ; 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. / A Phase I/II study evaluating escalating doses of recombinant human albumin-interferon-α fusion protein in chronic hepatitis C patients who have failed previous interferon-α-based therapy. In: Antiviral Therapy. 2006 ; Vol. 11, No. 1. pp. 35-45.
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abstract = "Albumin-interferon-α (IFN-α) is a novel 85.7-kDa recombinant protein consisting of IFN-α 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-α in IFN-α-experienced patients with chronic hepatitis C. Albumin-IFN-α was administered in 22 escalating doses (7-900 μg) 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-α had a favourable safety profile at doses up to 900 μg. 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 ≥28 days following a single injection of albumin-IFN-α at doses of ≥40 μg. Dose-dependent antiviral activity was observed in this IFN-α-experienced study population. Antiviral activity of ≥1.0-log reductions in HCV RNA was observed in 47{\%} (37/78) of patients in the 120- to 900-μg cohorts and in 59{\%} (16/27) in the 400- to 900-μg double-injection cohorts. These results support further clinical studies of albumin-IFN-α for the treatment of patients with chronic hepatitis C.",
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AU - Nelson, David R.

AU - Sulkowski, Mark S.

AU - Everson, Gregory T.

AU - Lambiase, Louis

AU - Wiesner, Rusell H.

AU - Dickson, Rolland C.

AU - Post, Anthony B.

AU - Redfield, Robert R.

AU - Davis, Gary L.

AU - Neumann, Avidan U.

AU - Osborn, Blaire L.

AU - Freimuth, William W.

AU - Subramanian, G. Mani

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