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

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-1

• Cunnion, K.
• Goss, J.
• Hair, P.
• Dell, L.
• Roberson, D.
• Thienel, U.
• Müller, M.
• Carstensen-Aurèche, S.
• Badorrek, P.
• Holz, O.
• Hohlfeld, J. M.