A randomized phase 1 study of the anti-interleukin-33 antibody tozorakimab in healthy adults and patients with chronic obstructive pulmonary disease

Clin Pharmacol Ther. 2023 Dec 19. doi: 10.1002/cpt.3147. Online ahead of print.ABSTRACTTozorakimab is a human monoclonal antibody that neutralizes interleukin (IL)-33. IL-33 is a broad-acting epithelial 'alarmin' cytokine upregulated in lung tissue of patients with chronic obstructive pulmonary disease (COPD). This first-in-human, phase 1, randomized, double-blind, placebo-controlled study (NCT03096795) evaluated the safety, tolerability, pharmacokinetics, immunogenicity, target engagement, and pharmacodynamics of tozorakimab. This was a three-part study. In part 1, 56 healthy participants with a history of atopy received single escalating doses of either intravenous or subcutaneous tozorakimab or placebo. In part 2, 24 patients with COPD received multiple escalating doses of subcutaneous tozorakimab or placebo. In part 3, 8 healthy Japanese participants received a single intravenous dose of tozorakimab or placebo. The safety data collected included treatment-emergent adverse events (TEAEs), vital signs, and clinical laboratory parameters. Biological samples for pharmacokinetics, immunogenicity, target engagement, and pharmacodynamic biomarker analyses were collected. No meaningful differences in the frequencies of TEAEs were observed between the active and placebo arms. Three tozorakimab-treated participants with COPD experienced treatment-emergent serious adverse events. Subcutaneous or intravenous tozorakimab demonstrated linear, time-independent pharmacokinetics with a me...
Source: Clinical Pharmacology and Therapeutics - Category: Drugs & Pharmacology Authors: Source Type: research