[更多DV - 601的信息 - Stephen]
http://www1.easl.eu/easl2011/program/Posters/Abstract628.htm
Poster Presentations Session Title: Category 07c: Viral Hepatitis B & D: Clinical (therapy, new compounds, resistance)
Presentation Date: 01 APR, 2011
TREATMENT OF CHRONIC HEPATITIS B INFECTION WITH DV-601, A THERAPEUTIC VACCINEM. Spellman1*, J.T. Martin2
1Clinical Research and Development, 2Dynavax Technologies, Berkeley, CA, USA. *[email protected]
Therapeutic vaccines may promote the resolution of chronic hepatitis B infection (CHB) through the stimulation of specific cytotoxic T-lymphocyte and B-cell antibody responses to dominant hepatitis B virus (HBV)-antigens. DV-601 is comprised of recombinant HBV surface antigen (HBsAg) and HBV core antigen (HBcAg), with adjuvant. In this initial dose-escalation study of DV-601 in treatment-naïve or treatment-tolerant adult patients with CHB, patients received 6 intramuscular doses of DV-601 (0.1, 0.25, or 0.5 mL) on Days 1, 15, 29, 57, 71, and 85. Of the 14 enrolled patients, 8 were HBV e-antigen positive and were treatment-naïve; 6 patients, all HBV e-antigen negative, had been treated with nucleoside analog(s) prior to enrolling in the study. Oral entecavir therapy was initiated (and other nucleoside analog therapy was discontinued, if applicable) prior to the first DV-601 injection, and was continued daily during the study. The primary objective was to assess the safety and tolerability of DV-601 by the evaluation of local and systemic adverse events to Day 99, including changes in laboratory analyses. Secondary objectives were to evaluate virological response and immunogenicity of DV-601 based on HBV viral load, and humoral and T cell immunological responses. Fourteen patients were enrolled and completed all injections of DV-601. Injection site reactions were generally short-lived and resolved without treatment; systemic injection reactions including fatigue, malaise, chills, and headache were transient and rarely required intervention. Reductions in HBV DNA, and s and e antigen are apparent in all dose groups, and antibodies to s and e antigens developed in the higher dose groups. All patients developed an HBV-specific lymphoproliferative response; an HBc-specific interferon-gamma T cell response was noted in 2 of 6 patients who were e-antigen positive and had received the highest dose of DV-601. DV-601 appears to be a safe and well-tolerated therapeutic vaccine for the treatment of CHB, and virological response is evident. |