RLS-0071, a novel anti-inflammatory agent, significantly reduced inflammatory biomarkers in a randomised human evaluation of mechanisms and safety study

ERJ Open Res. 2024 Sep 16;10(4):01006-2023. doi: 10.1183/23120541.01006-2023. eCollection 2024 Jul.

Abstract

Background: 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 hypothesised that RLS-0071 inhibits a temporary neutrophil-mediated inflammation in the lungs induced by inhalation of low-dose lipopolysaccharide (LPS) in healthy participants.

Methods: 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-1 loading dose followed by two doses of 40 mg·kg-1) RLS-0071 i.v. or placebo (saline) every 8 h. Biomarkers evaluating inflammatory responses, with absolute neutrophil counts in induced sputum as the primary end-point, were collected before and at 6 and 24 h after LPS challenge.

Results: 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-0071 versus placebo at 24 h.

Conclusion: 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.