Complete Removal of Extracellular IgG Antibodies in a Randomized Dose-Escalation Phase I Study with the Bacterial Enzyme IdeS – A Novel Therapeutic Opportunity
Fig 9
Anti-IdeS antibodies were followed before and throughout the study.
Human serum samples were analyzed using the IdeS-ImmunoCAP (Thermo Fisher Scientific) on a Phadia 250 instrument. The cut off (LLOQ) for IgG was 2 mg/L. A) Samples from 130 human donors (reference) were compared to the 78 healthy human male subjects screened in this study (screening). The lines show median for the reference group (6.1 mg/L) and the screening group (10.6 mg/L). B) Kinetics of the anti-IdeS IgG levels shown as a mean for the 0.12 and 0.24 mg/kg BW groups (n = 8; mean ± SEM). No increase in anti-IdeS IgG is seen in any of the subjects prior to day 14. C) Anti-IdeS IgG levels shown for the separate groups at day 14 (nPlacebo = 9, n0.01 = 8, n0.04 = 4, n0.12 = 4 and n0.24 = 4), and D) at day 182 (nPlacebo = 5, n0.01 = 7, n0.04 = 4, n0.12 = 2 and n0.24 = 4). The subjects were asked to come back for an outside the study protocol sample on day 182. 17 out of 20 on active and 5 out of 9 on placebo volunteered. The lines show median level for each group. In C and D the groups were compared using Kruskal-Wallis, One-Way ANOVA, P = 0.0003 and P = 0.0082 respectively. The P-values shown in the graph represent comparisons of the mean rank of each dose-group with the placebo group using Dunn’s Multiple Comparison. The placebo group contains all subjects from all dose-groups treated with placebo.