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) PMID: 38490660

ADC Targets in Oncology

2026-04-10

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

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.

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.