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 hypothesized that RLS-0071 inhibits a temporary neutrophil-mediated inflammation in the lungs induced by inhalation of low-dose 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 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.
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.
Discussion/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.
Footnotes
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Conflict of interest: In accordance with our ethical obligation as researchers, we are reporting that J Goss, P Hair, U Thienel and K Cunnion are employed by ReAlta Life Sciences and receive funding in the form of salaries from ReAlta Life Sciences, a company that may be affected by the research reported in the enclosed paper. J M Hohlfeld reports grant support paid to his institution from AltamiraPharma GmbH, Astellas Pharma GmbH, AstraZeneca AB, Bayer AG, Beiersdorf AG, Boehringer Ingelheim Pharma GmbH & Co. KG, CSL Behring GmbH, Desitin Arzneimittel GmbH, EpiEndo Pharmaceuticals, F. Hoffmann-La Roche AG, Genentech, Inc., GlaxoSmithKline GmbH & Co. KG, Janssen Pharmaceutical NV, M&P Pharma AG, Novartis AG, ReAlta Life Sciences, Sanofi-Aventis Deutschland GmbH and UCB Pharma GmbH, personal fees for consultancy from Boehringer Ingelheim Pharma GmbH & Co. KG, Cureteq AG, Merck & Co, Inc., and Roche, personal fees for lectures from HAL Allergy Group and Novartis AG, and personal fees for board service from CSL Behring GmbH and Nocion.
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- Received January 3, 2024.
- Accepted April 23, 2024.
- Copyright ©The authors 2024
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