First-in-Human Study in Healthy Subjects with the Noncytotoxic Monoclonal Antibody OSE-127, a Strict Antagonist of IL-7Rα
| Autor: | Nicolas Poirier, Irène Baccelli, Lyssia Belarif, Riad Abès, Géraldine Teppaz, Caroline Mary, Sonia Poli, Claudia Fromond, Isabelle Girault, Sabrina Pengam, Emilienne Soma, Fanny De Sa, Jean-Pascal Conduzorgues, Cécile Braudeau, Regis Josien, Bram Volckaert, Dominique Costantini, Frédérique Corallo |
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| Rok vydání: | 2023 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 210:753-763 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | OSE-127 is a humanized mAb 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 noncytotoxic. In this work, 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 i.v. administration (0.002–10 mg/kg), a single s.c. treatment group (1 mg/kg), and two double i.v. injection groups (6 or 10 mg/kg). Subjects were followed during 100 d after two i.v. 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, highlights that OSE-127 may show clinical activity in IL-7R pathway–involved diseases. |
| Databáze: | OpenAIRE |
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