2. Academic Validation
  3. 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)

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)

  • BMJ Open. 2024 Mar 15;14(3):e076142. doi: 10.1136/bmjopen-2023-076142.
Ranjani Somayaji 1 2 3 4,  David R Luke 5,  Arthur Lau 6 5,  Rahmet Guner 7,  Ŏ Fehmi Tabak 7,  Mark Hepokoski 8 9,  Nancy Gardetto 8 9,  Steven A Conrad 10,  Sunil D Kumar 11,  Kalyan Ghosh 12,  Stephen M Robbins 13 14 15,  Donna L Senger 13 14 15,  Daisy Sun 5,  Rachel K S Lim 6,  Jonathan Liu 6,  Fatma Eser 16,  Ridvan Karaali 7,  Alain Tremblay 6 4,  Daniel Muruve 6 2 4
Affiliations

Affiliations

  • 1 Department of Medicine, University of Calgary, Calgary, Alberta, Canada [email protected].
  • 2 Department of Microbiology, Immunology and Infectious Disease, University of Calgary, Calgary, Alberta, Canada.
  • 3 Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada.
  • 4 Snyder Insititute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada.
  • 5 Arch Biopartners Inc, Toronto, Ontario, Canada.
  • 6 Department of Medicine, University of Calgary, Calgary, Alberta, Canada.
  • 7 Istanbul University-Cerrahpasa School of Medicine, Ankara, Turkey.
  • 8 University of California San Diego Medical Center, San Diego, California, USA.
  • 9 Veterans Administration San Diego Healthcare System, San Diego, California, USA.
  • 10 Departments of Medicine, Pediatrics, and Emergency Medicine, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA.
  • 11 Broward Health Medical Center, Ft. Lauderdale, Florida, USA.
  • 12 Inference Inc, Chesterbrook, Pennsylvania, USA.
  • 13 Department of Oncology, University of Calgary, Calgary, Alberta, Canada.
  • 14 Lady Davis Institute for Medical Research - Jewish General Hospital, Montreal, Quebec, Canada.
  • 15 Gerald Bronfman Department of Oncology, McGIll University, Montreal, Quebec, Canada.
  • 16 Departments of Medicine, Infectious Diseases and Clinical Microbiology - Ankara City Hospital, Ankara Yildirim Beyazit University, Ankara, Turkey.
PMID: 38490660 DOI: 10.1136/bmjopen-2023-076142
Abstract

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 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.

Design: Phase 2a randomised, placebo-controlled, double-blinded, trial.

Setting: Hospitals in Canada, Turkey and the USA.

Participants: A total of 61 subjects with moderate-to-severe 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 ventilation-free 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 (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.

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.

Keywords

COVID-19; Clinical Trial; INFECTIOUS DISEASES; Safety.

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