First clinical trials of a new heteropolymer technology agent in normal healthy volunteers and patients with systemic lupus erythematosus: safety and proof of principle of the antigen-heteropolymer ETI-104

Background: The heteropolymer technology was developed to remove pathogens from the circulation. Objectives: To evaluate the safety and tolerability of a single administration and to establish proof of principle for ETI-104 in normal healthy volunteers (NHV) and patients with systemic lupus erythematosus (SLE) Methods: The drug was given intravenously to 11 NHV and six patients with SLE. Over 28 days, vital signs were noted, a haematological and chemical analysis of blood and urine was carried out, and adverse events were recorded. CR1 receptor numbers, the ability of antigen based heteropolymers to bind to red blood cells (RBCs), and the clearance of high avidity and total anti-dsDNA antibodies were measured by Farr assays and FACS analysis. Results: No safety measure differed significantly from normal in both groups; no drug related serious adverse events occurred. ETI-104 rapidly bound to RBCs in NHV and patients with SLE. Binding of the drug to RBCs of patients with SLE also caused a rapid reduction of circulating anti-dsDNA antibodies in the plasma 15 minutes after administration, with a maximum reduction of 55% ( range 43262). At 28 days statistically significant decreases were maintained in three patients, while in the other three the values had returned to baseline levels. Conclusion: These clinical trials established the safety and the proof of principle of the new immunoconjugate ETI-104. This provides the basis for further development of this technology for numerous indications - for example, therapeutic options for autoimmune diseases or viral and bacterial infections.