Multicentre, randomised, double-blind, placebo-controlled, proof of concept study of LSALT peptide as prevention of acute respiratory distress syndrome and acute kidney injury in patients infected with SARS-CoV-2 (COVID-19)

• Published in: BMJ open Vol. 14; no. 3; p. e076142
• Main Authors: Somayaji, Ranjani, Luke, David R, Lau, Arthur, Guner, Rahmet, Tabak, Ŏ Fehmi, Hepokoski, Mark, Gardetto, Nancy, Conrad, Steven A, Kumar, Sunil D, Ghosh, Kalyan, Robbins, Stephen M, Senger, Donna L, Sun, Daisy, Lim, Rachel K S, Liu, Jonathan, Eser, Fatma, Karaali, Ridvan, Tremblay, Alain, Muruve, Daniel
• Format: Journal Article
• Language: English
• Published: England British Medical Journal Publishing Group 15.03.2024; BMJ Publishing Group LTD; BMJ Publishing Group
• Series: Original research
• Subjects: Acute Kidney Injury - prevention & control; Clinical Trial; Consent; COVID-19; COVID-19 vaccines; Double-Blind Method; Dyspnea; FDA approval; Hematology; Hepatitis; Humans; Illnesses; Immunization; Infections; Infectious Diseases; Inflammation; Kidneys; Leukocytes; Liver; Lungs; Neutrophils; Pandemics; Patient safety; Peptides; Pharmacists; Proof of Concept Study; Regulatory agencies; Respiratory distress syndrome; Respiratory Distress Syndrome - prevention & control; Respiratory Insufficiency; Safety; SARS-CoV-2; Sea level; Sepsis; Severe acute respiratory syndrome coronavirus 2; Treatment Outcome; Vital signs; United States > US; Turkey; COVID-19; INFECTIOUS DISEASES; Safety; Clinical Trial
• ISSN: 2044-6055; 2044-6055
• DOI: 10.1136/bmjopen-2023-076142

ObjectiveDipeptidase-1 (DPEP-1) is a recently discovered leucocyte adhesion receptor for neutrophils and monocytes in the lungs and kidneys and serves as a potential therapeutic target to attenuate inflammation in moderate-to-severe COVID-19. We aimed to evaluate the safety and efficacy of the DPEP-1 inhibitor, LSALT peptide, to prevent specific organ dysfunction in patients hospitalised with COVID-19.DesignPhase 2a randomised, placebo-controlled, double-blinded, trial.SettingHospitals in Canada, Turkey and the USA.ParticipantsA total of 61 subjects with moderate-to-severe COVID-19.InterventionsRandomisation to LSALT peptide 5 mg intravenously daily or placebo for up to 14 days.Primary and secondary outcome measuresThe primary endpoint was the proportion of subjects alive and free of respiratory failure and/or the need for renal replacement therapy (RRT). Numerous secondary and exploratory endpoints were assessed including ventilation-free days, and changes in kidney function or serum biomarkers.ResultsAt 28 days, 27 (90.3%) and 28 (93.3%) of subjects in the placebo and LSALT groups were free of respiratory failure and the need for RRT (p=0.86). On days 14 and 28, the number of patients still requiring more intensive respiratory support (O2 ≥6 L/minute, non-invasive or invasive mechanical ventilation or extracorporeal membrane oxygenation) was 6 (19.4%) and 3 (9.7%) in the placebo group versus 2 (6.7%) and 2 (6.7%) in the LSALT group, respectively (p=0.14; p=0.67). Unadjusted analysis of ventilation-free days demonstrated 22.8 days for the LSALT group compared with 20.9 in the placebo group (p=0.4). LSALT-treated subjects had a significant reduction in the fold expression from baseline to end of treatment of serum CXCL10 compared with placebo (p=0.02). Treatment-emergent adverse events were similar between groups.ConclusionIn a Phase 2 study, LSALT peptide was demonstrated to be safe and tolerated in patients hospitalised with moderate-to-severe COVID-19.Trial registration numberNCT04402957.