First-in-Human Study in Healthy Subjects with the Non-Cytotoxic Monoclonal Antibody OSE-127, a Strict Antagonist of the IL-7Rα

OSE-127 is a humanized monoclonal antibody targeting the IL-7Rα chain (CD127), under development for inflammatory and autoimmune disease treatment. It is a strict antagonist of the IL-7R pathway, is not internalized by target cells and is non-cytotoxic. Here, a first-in-human, phase I, randomized, double-blind, placebo-controlled, single-center study was carried out to determine the safety, pharmacokinetics, pharmacodynamics, and immunogenicity of OSE-127 administration.Sixty-three healthy subjects were randomly assigned to nine groups: six single ascending dose groups with intravenous (IV) administration (0.002-10 mg/kg), a single subcutaneous treatment group (1 mg/kg), and two double IV injection groups (6 or 10 mg/kg). Subjects were followed during < 146 days. OSE-127’s pharmacokinetic half-life after a single dose increased from 4.6 days (1mg/kg) to 11.7 days (10 mg/kg) and, after a second dose, from 12.5 days (6 mg/kg) to 16.25 days (10 mg/kg). Receptor occupancy was ≥ 95% at doses ≥ 0.02 mg/kg and this saturation level was maintained >100 days after two IV infusions at 10 mg/kg. IL-7 consumption was inhibited by OSE-127 administration, as demonstrated by a decreased IL-7 pathway gene signature in peripheral blood cells and by ex-vivo T-lymphocyte restimulation experiments. OSE-127 was well tolerated, with no evidence of cytokine-release syndrome and no significant alteration of blood lymphocyte counts or subset populations.Altogether, the observed lack of significant lymphopenia or serious adverse events, concomitant with the dose-dependent inhibition of IL-7 consumption by target cells highlight that OSE-127 may show clinical activity in IL-7R pathway-involved diseases. 22 paired samples (at baseline, Day15, Day57) were collected on Day 15 after administration, and 4 paired samples were collected on Day 57 for transcriptomic analysis to follow the antiIL7R signature on Healthy volunteers.