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)
Dr Ranjani Somayaji, David R Luke, Arthur Lau, Rahmet Guner, Ŏ Fehmi Tabak, Mark Hepokoski, Nancy Gardetto, Steven A Conrad, Sunil D Kumar, Kalyan Ghosh, Stephen M Robbins, Donna L Senger, Daisy Sun, Rachel K S Lim, Jonathan Liu, Fatma Eser, Ridvan Karaali, Alain Tremblay, Daniel Muruve
BMJ Open, doi:10.1136/bmjopen-2023-076142
Objective Dipeptidase-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 moderateto-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. Design Phase 2a randomised, placebo-controlled, doubleblinded, trial. Setting Hospitals in Canada, Turkey and the USA. Participants A total of 61 subjects with moderate-tosevere COVID-19. Interventions Randomisation to LSALT peptide 5 mg intravenously daily or placebo for up to 14 days. Primary and secondary outcome measures The 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 ventilationfree days, and changes in kidney function or serum biomarkers. Results At 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 (O 2 ≥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). Treatmentemergent adverse events were similar between groups.
Conclusion In a Phase 2 study, LSALT peptide was demonstrated to be safe and tolerated in patients hospitalised with moderate-to-severe COVID-19. Trial registration number NCT04402957. .
Competing interests DRL, DS, KG and AL are employed by Arch Biopartners Inc. DRL, AL, SMR and DLS hold equity positions in Arch Biopartners. SMR, DLS, AL and DM have patents issued and pending in the areas of dipeptidase-1 and the LSALT peptide. DM is the acting chief science officer for Arch Biopartners and is compensated with an equity position. DM has received research funding from Arch Biopartners. All other authors have no competing interests. Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research. Patient consent for publication Not applicable.
Ethics approval The study was conducted in accordance with the ethical principles that have their origins in the Declaration of Helsinki, in compliance with the approved protocol, good clinical practice and applicable regulatory requirements. The study protocol, associated amendments and informed consents in the USA and Canada were approved by each hospital's institutional Research Ethics Committee (ethics approval number: Advarra CIRB MOD00749358 20 August 2020) and respective national regulatory agencies before enrolment began. Ethics approval in Turkey was issued by the Ministry of Health and the two participating institutions. Participants gave informed consent to participate in the study before taking part. Provenance and peer review Not commissioned; externally peer reviewed. Data availability statement Data are available..
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doi:10.1002/dmrr.3377DOI record:
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