Other pharmacodynamic assays
allergic toxicity, anaphylaxis, anti-FRα
ADVERSE EVENTS, ANAPHYLAXIS, INFUSION REACTION
No features of anaphylaxis or other manifestation of allergic toxicity were observed in preclinical animal models, but in addition to the risk mitigation steps described above, serial measurements of serum tryptase were included in this trial. Tryptase is released by degranulation of activated effector cells, and elevation is characteristic of anaphylaxisPatient specimens were also collected for pharmacodynamic analysis. Serum samples were collected pre- and post-dose for multiplex analysis of a cytokine panel (Randox) relevant to IgE biologyAnti-drug antibody (ADA) samples were drawn at baseline and 2 and 5 weeks following initiation of weekly dosing. Additional samples were collected 28 days after the last dose was administered and following any suspected infusion reaction. Serum samples were stored frozen at −80 °C prior to analysis using a bridging ELISA assay with MOV18 IgE to capture, and biotinylated MOv18 IgE followed by streptavidin-HRP (BD 554066) to detect the presence of ADAs. A confirmatory assay was performed on all positive samples, pre-incubating with drug to distinguish specific responses from false positives.Further blood samples were drawn at baseline, 3 weeks following initiation of weekly dosing and 28 days after the last dose, as well as following any observed adverse events. Serum was separated and stored at −80°C prior to evaluation of circulating soluble FRα and anti-FRα antibodies by ELISA, as previously described