Background: The glycosphingolipid α-galactosylceramide (α-GalCer) is known to stimulate invariant natural killer T-cells (iNKTs) and is able to induce powerful antiviral immune responses. The present dose-escalating randomized placebo-controlled Phase I/II trial aimed to investigate antiviral activity and safety of α-GalCer as a novel class of treatment for chronic hepatitis B patients. Methods: Patients were randomly assigned to 0.1 μg/kg (n=8), 1 μg/kg (n=6) or 10 μg/kg (n=6) α-GalCer or placebo (n=7) treatment. Results: Almost all α-GalCer-treated patients showed a rapid and strong decrease in natural killer T-cell (NKT) numbers. Patients with high baseline NKT numbers showed immune activation, including natural killer cell activation, increased serum tumour necrosis factor-α and interleukin-6 levels, and development of fever. Three patients demonstrated a transient decrease in hepatitis B virus (HBV) DNA. Only one α-GalCer-treated patient had a sustained decrease in HBV DNA at the end of follow-up. Four patients discontinued therapy because of fever shortly after drug administration. No significant side effects were observed. Conclusions: α-GalCer (0.1-10 μg/kg) used as monotherapy for chronic hepatitis B infection resulted in a strong decrease of NKTs, but did not clearly affect HBV DNA and alanine aminotransferase levels. α-GalCer was poorly tolerated and is unlikely to be suitable as an alternative monotherapy to the current treatment regimen.

Additional Metadata
Persistent URL,
Journal Antiviral Therapy
Woltman, A.M, ter Borg, M.J, Binda, R.S, Sprengers, D, von Blomberg, B.M.E, Scheper, R.J, … Janssen, H.L.A. (2009). α-Galactosylceramide in chronic hepatitis B infection: Results from a randomized placebo-controlled Phase I/ II trial. Antiviral Therapy, 14(6), 809–818. doi:10.3851/IMP1295