RLS-0071, a novel anti-inflammatory agent, significantly reduced inflammatory biomarkers in a randomised human evaluation of mechanisms and safety study
K. Cunnion, J. Goss, Pamela Hair, L. Dell, Destrey Roberson, U. Thienel, Meike Mϋller, Saskia Carstensen-Aurèche, P. Badorrek, Olaf Holz, Jens M Hohlfeld
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引用次数: 0
Abstract
This study was a randomised, double-blind, placebo-controlled study intended to establish the translatability of the RLS-0071 mechanisms of action from animal disease models to humans by inhibiting neutrophil-mediated inflammation at the tissue level and major inflammatory biomarkers. We hypothesized that RLS-0071 inhibits a temporary neutrophil-mediated inflammation in the lungs induced by inhalation of low-dose LPS in healthy participants.Participants were randomised to one of three arms to receive inhaled LPS followed by three doses of either low-dose (10 mg·kg−1) or high-dose (120 mg·kg−1loading dose followed by 2 doses of 40 mg·kg−1) RLS-0071 IV or placebo (saline) every 8 h (Q8H). Biomarkers evaluating inflammatory responses, with absolute neutrophil counts in induced sputum as the primary endpoint, were collected before and at 6 and 24 h after LPS challenge.Active treatment with RLS-0071 showed a similar safety profile to participants receiving placebo. RLS-0071 significantly decreased the numbers of neutrophils in sputum at 6 h post LPS by approximately half (p=0.04). Neutrophil effectors myeloperoxidase, neutrophil elastase, and Interleukin-1β in sputum were also significantly decreased at 6 h for RLS-0071 compared with placebo. Several biomarkers showed trends suggesting sustained decreases for RLS-0071versusplacebo at 24 h.This clinical trial demonstrated that RLS-0071 was safe and well tolerated and modulated neutrophil-mediated inflammation in humans after inhaled LPS challenge, consistent with results from prior animal model studies.
期刊介绍:
ERJ Open Research is a fully open access original research journal, published online by the European Respiratory Society. The journal aims to publish high-quality work in all fields of respiratory science and medicine, covering basic science, clinical translational science and clinical medicine. The journal was created to help fulfil the ERS objective to disseminate scientific and educational material to its members and to the medical community, but also to provide researchers with an affordable open access specialty journal in which to publish their work.