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)
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...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2024-03-01
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| Series: | BMJ Open |
| Online Access: | https://bmjopen.bmj.com/content/14/3/e076142.full |
| _version_ | 1797260778809589760 |
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| author | Alain Tremblay Ranjani Somayaji Arthur Lau Fatma Eser Rahmet Guner David R Luke 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 Ridvan Karaali Daniel Muruve |
| author_facet | Alain Tremblay Ranjani Somayaji Arthur Lau Fatma Eser Rahmet Guner David R Luke 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 Ridvan Karaali Daniel Muruve |
| author_sort | Alain Tremblay |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-24T23:30:44Z |
| format | Article |
| id | doaj.art-ce794de0f6f943398e235ef10b530862 |
| institution | Directory Open Access Journal |
| issn | 2044-6055 |
| language | English |
| last_indexed | 2024-04-24T23:30:44Z |
| publishDate | 2024-03-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open |
| spelling | doaj.art-ce794de0f6f943398e235ef10b5308622024-03-15T15:50:08ZengBMJ Publishing GroupBMJ Open2044-60552024-03-0114310.1136/bmjopen-2023-076142Multicentre, 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)Alain Tremblay0Ranjani Somayaji1Arthur Lau2Fatma Eser3Rahmet Guner4David R Luke5Ŏ Fehmi Tabak6Mark Hepokoski7Nancy Gardetto8Steven A Conrad9Sunil D Kumar10Kalyan Ghosh11Stephen M Robbins12Donna L Senger13Daisy Sun14Rachel K S Lim15Jonathan Liu16Ridvan Karaali17Daniel Muruve18Department of Medicine, University of Calgary, Calgary, Alberta, CanadaDivision of Infectious Diseases, University of Calgary, Calgary, Alberta, CanadaDepartment of Medicine, University of Calgary, Calgary, Alberta, CanadaInfectious Diseases and Clinical Microbiology Clinic, Ankara Yıldırım Beyazıt University, Ankara City Hospital, Ankara, TurkeyInfectious Diseases and Clinical Microbiology Clinic, Ankara Yıldırım Beyazıt University, Ankara City Hospital, Ankara, TurkeyArch Biopartners Inc, Toronto, Ontario, CanadaIstanbul University–Cerrahpasa School of Medicine, Ankara, TurkeyVeterans Administration San Diego Healthcare System, San Diego, California, USAUniversity of California San Diego Medical Center, San Diego, California, USADepartments of Medicine, Pediatrics, and Emergency Medicine, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USABroward Health Medical Center, Ft. Lauderdale, Florida, USAInference Inc, Chesterbrook, Pennsylvania, USADepartment of Oncology, University of Calgary, Calgary, Alberta, CanadaDepartment of Oncology, University of Calgary, Calgary, Alberta, CanadaArch Biopartners Inc, Toronto, Ontario, CanadaDepartment of Medicine, University of Calgary, Calgary, Alberta, CanadaDepartment of Medicine, University of Calgary, Calgary, Alberta, CanadaIstanbul University–Cerrahpasa School of Medicine, Ankara, TurkeyDepartment of Medicine, University of Calgary, Calgary, Alberta, CanadaObjective 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.https://bmjopen.bmj.com/content/14/3/e076142.full |
| spellingShingle | Alain Tremblay Ranjani Somayaji Arthur Lau Fatma Eser Rahmet Guner David R Luke 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 Ridvan Karaali Daniel Muruve 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 |
| title | 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) |
| title_full | 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) |
| title_fullStr | 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) |
| title_full_unstemmed | 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) |
| title_short | 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) |
| title_sort | 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 |
| url | https://bmjopen.bmj.com/content/14/3/e076142.full |
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