Safety and Dose-finding Study of DC-TAB in Healthy Subjects

This study is a double-blind, randomized, placebo-controlled, dose-escalation study of DC-TAB in healthy human volunteers. DC-TAB is a solution of the small heat-shock protein alpha B-crystallin for intravenous injection, designed to induce selective immunological tolerance as a treatment for multiple sclerosis. In this first-in-man study, DC-TAB is administered to healthy subjects in varying doses and for a varying number of times, after which safety and tolerability is evaluated, as well as the impact of the treatment on antigen-specific responses by peripheral blood T cells and serum antibodies. Blood samples are additionally collected to measure serum concentrations of DC-TAB, and to determine the rate of clearance from the circulation. The study is double blind and placebo-controlled to strengthen the significance especially of immunological evaluations. The study consists of two parts. In Part 1, subjects receive a single dose of DC-TAB or placebo whereas in Part 2, (different) subjects receive DC-TAB or placebo on 3 consecutive days. In Part 1, four groups of subjects (n=10) are studied in a single dose, dose-escalation design. Each group of subjects are randomized to receive either DC-TAB (n=8) or placebo (n=2) once. In Part 2, three groups of subjects (n=12) are studied in a multiple dose, dose-escalation design. Each group of subjects are randomized to receive either DC-TAB (n=9) or placebo (n=3) once daily on 3 consecutive days. The next higher dose group in each part of the study only starts once safety data up to 4 days for Part 1, up to 8 days for Part 2 of the previous dose group have been reviewed and have raised no safety concerns. Part 2 is started once all safety data of Part 1 have been reviewed. Immunological effects of the treatments are evaluated over a period of 28 days.