RLS-0071, a Novel Anti-inflammatory Agent, Significantly Reduced Inflammatory Biomarkers in a Randomised Human Evaluation of Mechanisms and Safety Study

Overview

Journal ERJ Open Res

Specialty Pulmonary Medicine

Date 2024 Sep 17

PMID 39286057

Authors

Kenji Cunnion

Jessica Goss

Pamela Hair

Linda Dell

Destrey Roberson

Ulrich Thienel

Meike Muller

Saskia Carstensen-Aureche

Philipp Badorrek

Olaf Holz

Jens M Hohlfeld

Affiliations

Soon will be listed here.

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) or high-dose (120 mg·kg loading dose followed by two doses of 40 mg·kg) RLS-0071 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 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.

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