There was a poster on IL-12 and HCV at ICAAC. This
article may be of interest.
A Phase I/II Study of Recombinant Human Interleukin-12 in Patients With Chronic Hepatitis C
Hepatology, April 1999, p. 1280-1287, Vol. 29, No. 4
Stefan Zeuzem1, Uwe Hopf2, Vicente Carreno3, Moisés Diago4, Mitchell Shiffman5, Stefan Grüne6, Francis J. Dudley7, Ashok Rakhit8, Karen Rittweger8, Sing Hiem Yap9, Raymond S. Koff10, and Howard C. Thomas11
>From the 1Medizinische Klinik II, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt, Germany; 2Universitätsklinikum Charité, Campus Virchow-Klinikum, Berlin, Germany; 3Fundación Jiménez Díaz, Department of Hepatology, Madrid, Spain; 4Hospital General, Valencia, Spain; 5Medical College of Virginia, Richmond, VA; 6Innere Medizin I, Klinikum der Universität, Regensburg, Germany; 7Alfred Hospital, Prahran, Victoria, Australia; 8Hoffman-La Roche, Nutley, NJ; 9University Hospital Gasthuisberg, Leuven, Belgium; 10MetroWest Medical Center, Framingham, MA; and 11St. Mary's Hospital, London, UK.
Interleukin-12 (IL-12) plays a central role in mounting an effective cellular immune response directed towards elimination of intracellular pathogens. The present open-label, multicenter, dose-escalation phase I/II study was designed to assess tolerability, pharmacokinetics, pharmacodynamics, and efficacy of subcutaneously administered recombinant human interleukin-12 (rHuIL-12) in the treatment of chronic hepatitis C. Sixty patients (42 men, 18 women, aged 24-60) were treated with 0.03 µg/kg (n = 16), 0.1 µg/kg (n = 14), 0.25 µg/kg (n = 15), or 0.5 µg/kg rHuIL-12 (n = 15) for 10 consecutive weeks. rHuIL-12 was generally well tolerated, with 2 patients (3.3%) being withdrawn from treatment for adverse events. Treatment was associated with temporary decreases in neutrophils and lymphocyte counts and with elevations in serum transaminases and bilirubin. Serum IL-12 levels observed were higher at 0.5 µg/kg compared with 0.25 µg/kg doses, suggesting a dose-related increase in systemic exposure of IL-12. Measurable levels of interferon gamma (IFN-) were also observed at the highest dose of 0.5 µg/kg. At the end of treatment hepatitis C virus (HCV) RNA was detectable in all patients. A more than 50% decrease in pretreatment HCV RNA levels was observed in 3 of 16 patients of the 0.03-µg/kg dose group, in 3 of 14 of the 0.10-µg/kg dose group, in 6 of 15 of the 0.25-µg/kg dose group, and in 8 of 15 patients of the 0.5-µg/kg dose group. Although in several cases serum alanine transaminase (ALT) levels decreased either during or after treatment, ALT normalization was observed in only 4 patients at the end of treatment and in 5 patients at the end of follow-up. Significant anti-rHuIL-12 antibody titers were not detectable in any patient. In conclusion, antiviral activity of rHuIL-12 in patients with chronic hepatitis C does not appear advantageous in comparison with other currently available treatments.