To evaluate the proportion of subjects alive and free of respiratory failure (e.g. need for non-invasive or invasive mechanical ventilation, high flow oxygen, or ECMO) and free of the need for continued renal replacement therapy (RRT) on Day 28. The need for continued RRT at Day 28 will be defined as either dialysis in the past 3 days (Day 26, 27, or 28) or an eGFR on Day 28 \<10 mL/min/1.73 m2.
This study is a parallel group, randomized, third-party blinded, multicenter study to assess safety and efficacy of LSALT peptide versus placebo in hospitalized patients with confirmed infection or recent confirmed infection with complications associated with COVID-19. Following screening and after establishing baseline parameters such as lung and renal function, clinical chemistries, coagulation, hematology, and urinalysis, and satisfying all inclusion and exclusion criteria, patients will be randomized to one of two blinded treatment regimens: 1. 100 mL of 5 mg IV LSALT peptide infusion over 2 hours daily 2. 100 mL drug-free IV saline infusion over 2 hours daily. Thirty (30) patients will be randomized to active drug (LSALT peptide) and 30 patients will be randomized to matching placebo. This study will be third-party blind with only the Pharmacist at the site unblinded for the purpose of preparing drug/placebo for injection. Patients will be followed for safety and efficacy up to Day 28, with Day 1 being the day of randomization to assess safety. After assessing the risk of ARDS and satisfying all inclusion and exclusion criteria, the patient will be randomized to 5 mg LSALT peptide or blinded placebo to be given intravenously once daily for a maximum of 14 days. Physical and respiratory examinations, vital signs, and adverse events will be recorded throughout the study, including Day 28 (EOS). Blood chemistries, hematology, coagulation, urinalysis, ECG, SARS-CoV-2 tests, eGFR, and chest x-ray (CXR) will be assessed at Day 1 (Screening/Baseline) prior to initiation of study drug, and on Day 3, EOT, and at EOS, as well as when clinically indicated. The ECG at EOS will only be obtained if clinically indicated. An additional CXR will be obtained at time of clinical improvement. Cytokines/biomarkers and pharmacokinetics (PK) will be assessed at Day 1 (Screening/Baseline) prior to initiation of study drug, at 1 (mid-dose) and 2 hours (end of infusion) of drug therapy on Days 1, 3, EOT, and a single blood sample at EOS for cytokines/biomarkers only. Where applicable, a urinary pregnancy test will be obtained at Screening in women of childbearing potential. Questionnaires (APACHE II, SOFA) will be obtained at Baseline, Day 3, EOT, and EOS; venous blood gas (VBG) or HCO3 (bicarbonate) levels may be substituted for arterial blood gas (ABG) if it is considered standard-of-care (SOC) or in the patient's best interest, and results in comparable APACHE II and SOFA scores. Other questionnaires (Berlin Definition and modified Medical Research Council Dyspnea Scale) will be assessed at Baseline, Day 3, EOT, and EOS. IgG, IgA, and IgM antiviral antibodies will be collected at Baseline and EOS. Patients will be maintained on the SOC per institutional guidelines, including prophylaxis or treatment of VTE, throughout the study. A Data and Safety Monitoring Board (DSMB) will evaluate patients on a continuing basis for primarily safety assessments. Per the DSMB Charter, the DSMB will meet at least monthly if not more frequently based upon enrollment throughout the study period.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
61
LSALT, a peptide drug with the sequence NH3-LSALTPSPSWLKYKAL-COOH, binds to dipeptidase-1 (DPEP-1) but does not inhibit its biologic enzymatic activity. LSALT peptide inhibits leukocyte recruitment in multiple experimental disease models through the direct inhibition of leukocyte adhesion to DPEP-1 present in lungs, kidney, and liver.
0.9% saline solution
VA San Diego Healthcare System
San Diego, California, United States
Broward Health Medical Center
Fort Lauderdale, Florida, United States
LSU Health Shreveport
Shreveport, Louisiana, United States
University of Calgary - Foothills Medical Centre
Calgary, Alberta, Canada
University of Calgary - Peter Lougheed Centre
Calgary, Alberta, Canada
Ankara City Hospital
Ankara, Turkey (Türkiye)
Istanbul University Cerrahpasa
Istanbul, Turkey (Türkiye)
To Evaluate the Proportion of Subjects Alive and Free of Respiratory Failure and Free of the Need for Continued Renal Replacement Therapy (RRT) on Day 28 (as Per Protocol AB002 - Version 1, Dated 09JUNE2020)
Respiratory failure is defined as the need for non-invasive or invasive mechanical ventilation, high flow oxygen \[≥ 6 L/minute\], or ECMO. The need for continued RRT at Day 28 will be defined as either dialysis in the past 3 days (Day 26, 27, or 28) or an eGFR on Day 28 \<10 mL/min/1.73 m2.
Time frame: 28 days
All-cause Mortality
Time frame: 28 days
The Presence of and Severity of ARDS as an Ordinal Outcome of the Proportion of Patients Who Have None, Mild, Moderate, or Severe ARDS
Time frame: 28 days
Time to Each of Mild, Moderate, or Severe ARDS
Time frame: 28 days
The Number of Ventilation-free Days
Time frame: 28 days
Time on Nasal Cannula or Oxygen Mask
Time frame: 28 days
Length of Stay in ICU and Hospital (Admission to Discharge)
Time frame: 28 days
Virologic Clearance Rate
SARS-CoV2 testing by swab (nasopharyngeal, nasal, throat, sputum, or lower respiratory tract) at baseline (Day 1) and every 3 days thereafter until eradication
Time frame: 28 days
Worst PaO2/FiO2 Ratio Following Enrollment
The worst change in PaO2/FiO2 ratio from baseline (Day 1) over the course of the study was analyzed in patients. A negative value indicates a decrease in PaO2/FiO2 ratio compared to baseline.
Time frame: 28 days
Change in PaO2/FiO2 Ratio
Time frame: 28 days
Change in Baseline Modified Medical Research Council (mMRC) Score
Change in modified Medical Research Council score (0 to 4) with 4 being the most severe outcome. This scale is used to assess the degree of baseline functional disability due to dyspnea.
Time frame: 28 days
Change in Acute Physiologic Assessment and Chronic Health Evaluation (APACHE) II Score
Change in APACHE II score (0 to 71) with 71 being the most severe outcome
Time frame: 28 days
Change in Daily Sequential Organ Failure Assessment (SOFA) Score From Baseline in Patients With Extrapulmonary Organ Dysfunction
Change in SOFA score (0 to 4) with 4 being the most severe outcome
Time frame: 28 days
Change in Liver Function by Alanine Aminotransferase (ALT) Test
ALT measured in IU/L
Time frame: 28 days
Change in Liver Function by Aspartate Transferase (AST) Test
AST measured in IU/L
Time frame: 28 days
Change in Liver Function by Total Bilirubin Test
Total bilirubin measured in umol/L
Time frame: 28 days
Change in Renal Function by Serum Creatinine (SCr) Test
SCr measured in umol/L
Time frame: 28 days
Change in Activated Coagulation Time (ACT)
ACT measured in seconds
Time frame: 28 days
Change in Activated Partial Thromboplastin Time (aPTT)
aPTT measured in seconds
Time frame: 28 days
Change in Prothrombin International Normalized Ratio (INR)
Time frame: 28 days
Vasopressor-free Days
Time frame: 28 days
Change From Maximal Radiographic Damage to EOT
Time frame: 28 days
Change in Renal Function by Estimated Glomerular Filtration Rate (eGFR) Test
eGFR measured in ml/min/1.73m2
Time frame: 28 days
Change in Hs-troponin Levels
Time frame: 28 days
Change in Antiviral IgG, IgA, and IgM Levels
Immunoglobulins measured in mg/dL
Time frame: 28 days
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.