LSALT Peptide vs. Placebo to Prevent ARDS and Acute Kidne... | NCT04402957

NCT04402957

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Detailed Description

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:

100 mL of 5 mg IV LSALT peptide infusion over 2 hours daily
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.

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Placebo	Placebo Comparator	100 mL drug-free IV saline infusion over 2 hours daily	Drug: Placebo
LSALT	Experimental	100 mL of 5 mg IV LSALT peptide infusion over 2 hours daily	Drug: LSALT peptide

Interventions

Name	Type	Description	Arm Group Labels	Other Names
LSALT peptide	Drug	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.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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.	28 days

Secondary Outcomes

Measure	Description	Time Frame
All-cause Mortality		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		28 days

Other Outcomes

Measure	Description	Time Frame
Health Outcomes Endpoint: Total Healthcare Costs From Admission to Discharge Between Treatment Groups		28 days
Exploratory Endpoint: Change in Serum Cytokines Including IL-1a, IL-1b, and Ferritin Levels as Well as Other Exploratory Biomarkers Drawn at the Same Time as LSALT Peptide Concentrations

Eligibility Module

Eligibility Criteria

Inclusion Criteria (Amendment 3, 15FEB2021):

Male and female hospitalized patients between 18 and 80 years of age at time of consent.
Clinical and laboratory diagnosis of COVID-19 infection. Patients must be positive for the SARS-CoV-2 by Real-Time Reverse Transcriptase (RT)-PCR

Diagnostic Panel or have an existing complication secondary to SARS-CoV-2 infection which was positive within 2 weeks of entry into the study. Further, patients must have at least two of the following three symptoms:
- Fever (oral temperature ≥ 100.4 °F [> 38 °C]) with or without chills
- Dyspnea or difficulty breathing (≤ 2 on mMRC dyspnea scale)
- Nonproductive cough
- Or other signs and symptoms of established complications to SARS-CoV-2 infection (e.g. coagulopathy, cardiomyopathy, acute kidney injury, and/or acute liver injury) within the limits of Exclusion Criteria 8
Patients must present with moderate to severe illness as defined below:
- Moderate illness: Patients who have evidence of lower respiratory disease by clinical assessment or imaging and an oxygen saturation (SpO2) > 93% on room air at sea level
- Severe illness: Patients who have a respiratory frequency > 30 breaths per minute (bpm), SpO2 ≤ 93% on room air at sea level, ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) < 300, or lung infiltrates > 50%.
APACHE II score < 20 or establishment of survivability of the patient beyond 48 hours following randomization
Therapies which have been shown to be beneficial and are included in standard COVID-19 treatment guidelines (e.g. those of WHO or NIH, or institutional guidelines) are permitted
Sexually active women of child-bearing potential (WCBP) must be using a medically acceptable method of birth control throughout the study and for at least 1 day following the end of study, and have a negative urine pregnancy test at the Screening visit. A WCBP is defined as a female who is biologically capable of becoming pregnant. A medically acceptable method of birth control includes intrauterine devices in place for at least 3 months, surgical sterilization, or the implant. In patients who are not sexually active, abstinence is an acceptable form of birth control and urine will be tested per protocol. Women who are of nonchild-bearing potential, i.e., post-menopause, must have this condition captured in their medical history. Pregnant women and nursing mothers are excluded from this study.
Patient or LAR is available and willing to give written informed consent, after being properly informed of the nature and risks of the study and prior to engaging in any study-related procedures.

Exclusion Criteria:

Known sensitivity, allergy, or previous exposure to LSALT peptide.
Exposure to any investigational drug or device <90 days prior to entry into study.
Treatment with immunomodulators or immunosuppressant drugs, including but not limited to IL-6 inhibitors, TNF inhibitors, anti-IL-1 immunomodulators, and JAK inhibitors within five half-lives or 30 days (whichever is longer) prior to randomization and throughout the study period. However, should any of these treatments become standard-of-care and incorporated into clinical treatment guidelines (e.g. those of WHO or NIH), the treatment is permitted. Further, low-dose oral prednisone (<20 mg/day) and inhaled steroids (e.g. treatment of asthma) are allowed in the study.
Anticipated transfer to another hospital or medical center within 72 hours, which is not a study site.
Uncontrolled of poorly treated active hepatitis B (HBV), hepatitis C (HepC), or HIV infection. Those subjects who are positive for HBV, HepC, or HIV but are well-controlled with low viral loads are allowed to participate in this study:
- HBV low viral load defined as <20,000 IU/mL
- HepC low viral load defined as <800,000 IU/mL
- HIV low viral load defined as <5000 copies/mL
Participation in another drug or device study at any time during this study, for example:
- Ulinastatin 200,000 IU or greater
- High dose intravenous Vitamin C
- Budesonide and formoterol
- Bevacizumab to prevent ARDS
- Dornase alfa to reduce hypoxemia in ventilated trauma patients.
As indicated in the inclusion criteria, pregnant female patients are excluded from study. Further, female patients who are nursing are excluded from study.
Has any medical condition considered to be clinically significant and could potentially affect patient safety or study outcome, including but not limited to:
- Acute or chronic kidney disease (stage-4 or -5 renal impairment; eGFR<30 mL/min/1.73 m2 or hemodialysis)
- End-stage malignancy undergoing treatment
- Immunocompromised patients or those with medical/surgical conditions (e.g., solid organ transplantation) which require chronic immunosuppression
- Chronic hematologic disease which, in the opinion of the PI, prohibits the patient from entering into study
- Acute liver injury with AST and/or ALT levels greater than 3x ULN unless recent injury (within 2 weeks) likely due to COVID-19 infection
- History of coagulopathy within the last year as defined by abnormal ACT, aPTT, and/or PT/INR values at least 2-fold outside normal limits, and currently present at screening, and/or
- End-stage lung disease, acute lung injury, severe chronic obstructive pulmonary disease (COPD) as assessed by the GOLD criteria (GOLD Stage IV), or mechanical ventilation.

Contacts/Locations Module

Facility	Status	City	State	ZIP	Country	Contacts
VA San Diego Healthcare System		San Diego	California	92161	United States
Broward Health Medical Center

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
38490660	Derived	Somayaji R, Luke DR, Lau A, Guner R, Tabak OF, Hepokoski M, Gardetto N, Conrad SA, Kumar SD, Ghosh K, Robbins SM, Senger DL, Sun D, Lim RKS, Liu J, Eser F, Karaali R, Tremblay A, Muruve D. 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.

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo	100 mL drug-free IV saline infusion over 2 hours daily Placebo: 0.9% saline solution
FG001	LSALT	100 mL of 5 mg IV LSALT peptide infusion over 2 hours daily LSALT peptide: 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.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Uploaded Document Information

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Mar 17, 2021

Derived Section

Miscellaneous Info Module

Submission Tracking

Condition Browse Module

Intervention Browse Module

No data available

No data is available for this block.

Masking Info

Fold change from baseline cytokines measured in ng/mL

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	Placebo	100 mL drug-free IV saline infusion over 2 hours daily Placebo: 0.9% saline solution
BG001	LSALT	100 mL of 5 mg IV LSALT peptide infusion over 2 hours daily LSALT peptide: 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.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00057.3± 10.24 BG00162.3± 8.71 BG00259.8± 9.8

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00011 BG0019 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

BMI

Mean

Standard Deviation

kg/m2

Title

Denominators

Categories

Title	Measurements
	BG00032.29± 10.064 BG00131.72± 5.571 BG002

Chronic Lung Disease

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
	BG0003 BG0015 BG002

Chronic Renal Disease

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
	BG0001 BG0011 BG002

Cardiovascular Disease

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
	BG00015 BG00118 BG002

Diabetes

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
	BG00010 BG00113 BG002

PaO2/FiO2 Ratio

Mean

Standard Deviation

mmHg

Title

Denominators

Categories

Title	Measurements
	BG000247.956± 93.762 BG001247.097± 111.3844 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

The primary efficacy endpoint was the proportion of patients alive and free of respiratory failure (need for non-invasive or invasive mechanical ventilation, high flow oxygen, or ECMO) and free of the need for continued RRT on Day 28.

Posted

Count of Participants

Participants

28 days

ID	Title	Description
OG000	Placebo	100 mL drug-free IV saline infusion over 2 hours daily Placebo: 0.9% saline solution
OG001	LSALT	100 mL of 5 mg IV LSALT peptide infusion over 2 hours daily LSALT peptide: 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.

Units	Counts
Participants	OG00031 OG00130

Title

Denominators

Categories

Title	Measurements
	OG00028 OG00128

Secondary

All-cause Mortality

The all-cause mortality rate within 28 days from randomization was compared between the treatment groups using a CMH test.

Posted

Count of Participants

Participants

28 days

ID	Title	Description
OG000	Placebo	100 mL drug-free IV saline infusion over 2 hours daily Placebo: 0.9% saline solution
OG001	LSALT	100 mL of 5 mg IV LSALT peptide infusion over 2 hours daily LSALT peptide: 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.

Units	Counts
Participants	OG000

Secondary

The Presence of and Severity of ARDS as an Ordinal Outcome of the Proportion of Patients Who Have None, Mild, Moderate, or Severe ARDS

Number of patients with ARDS on Day 28 (EOS).

Posted

Count of Participants

Participants

28 days

ID	Title	Description
OG000	Placebo	100 mL drug-free IV saline infusion over 2 hours daily Placebo: 0.9% saline solution
OG001	LSALT	100 mL of 5 mg IV LSALT peptide infusion over 2 hours daily LSALT peptide: 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.

Units	Counts
Participants	OG000

Secondary

Time to Each of Mild, Moderate, or Severe ARDS

The proportion of patients that will develop ARDS at a given time point in the study.

Posted

Number

proportion of participants

28 days

ID	Title	Description
OG000	Placebo	100 mL drug-free IV saline infusion over 2 hours daily Placebo: 0.9% saline solution
OG001	LSALT	100 mL of 5 mg IV LSALT peptide infusion over 2 hours daily LSALT peptide: 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.

Units	Counts
Participants	OG000

Secondary

The Number of Ventilation-free Days

Comparison of ventilation-free days in placebo and LSALT treated patients.

Posted

Mean

Standard Deviation

days

28 days

ID	Title	Description
OG000	Placebo	100 mL drug-free IV saline infusion over 2 hours daily Placebo: 0.9% saline solution
OG001	LSALT	100 mL of 5 mg IV LSALT peptide infusion over 2 hours daily LSALT peptide: 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.

Units	Counts
Participants	OG000

Secondary

Time on Nasal Cannula or Oxygen Mask

Only patients that were on nasal cannula or oxygen mask were analysed.

Posted

Mean

95% Confidence Interval

hours

28 days

ID	Title	Description
OG000	Placebo	100 mL drug-free IV saline infusion over 2 hours daily Placebo: 0.9% saline solution
OG001	LSALT	100 mL of 5 mg IV LSALT peptide infusion over 2 hours daily LSALT peptide: 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.

Units	Counts
Participants	OG000

Secondary

Length of Stay in ICU and Hospital (Admission to Discharge)

Posted

Median

Full Range

days

28 days

ID	Title	Description
OG000	Placebo	100 mL drug-free IV saline infusion over 2 hours daily Placebo: 0.9% saline solution
OG001	LSALT	100 mL of 5 mg IV LSALT peptide infusion over 2 hours daily LSALT peptide: 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.

Units	Counts
Participants	OG000

Secondary

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

The virologic clearance rate (proportion of patients with a negative test result) at day 28 (EOS).

Posted

Count of Participants

Participants

28 days

ID	Title	Description
OG000	Placebo	100 mL drug-free IV saline infusion over 2 hours daily Placebo: 0.9% saline solution
OG001	LSALT	100 mL of 5 mg IV LSALT peptide infusion over 2 hours daily LSALT peptide: 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.

Units	Counts
Participants	OG000

Secondary

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.

Posted

Mean

95% Confidence Interval

mmHg

28 days

ID	Title	Description
OG000	Placebo	100 mL drug-free IV saline infusion over 2 hours daily Placebo: 0.9% saline solution
OG001	LSALT	100 mL of 5 mg IV LSALT peptide infusion over 2 hours daily LSALT peptide: 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.

Units	Counts
Participants	OG000

Secondary

Change in PaO2/FiO2 Ratio

Change from baseline to day 28 (EOS) in PaO2/FiO2 ratio.

Posted

Mean

Standard Deviation

mmHg

28 days

ID	Title	Description
OG000	Placebo	100 mL drug-free IV saline infusion over 2 hours daily Placebo: 0.9% saline solution
OG001	LSALT	100 mL of 5 mg IV LSALT peptide infusion over 2 hours daily LSALT peptide: 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.

Units	Counts
Participants	OG000

Secondary

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.

Change from baseline to day 28 (EOS) of modified Medical Research Council score.

Posted

Mean

Standard Deviation

score on a scale

28 days

ID	Title	Description
OG000	Placebo	100 mL drug-free IV saline infusion over 2 hours daily Placebo: 0.9% saline solution
OG001	LSALT	100 mL of 5 mg IV LSALT peptide infusion over 2 hours daily LSALT peptide: 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.

Units	Counts
Participants

Secondary

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

Change from baseline to day 28 (EOS) in APACHE II score.

Posted

Mean

Standard Deviation

score on a scale

28 days

ID	Title	Description
OG000	Placebo	100 mL drug-free IV saline infusion over 2 hours daily Placebo: 0.9% saline solution
OG001	LSALT	100 mL of 5 mg IV LSALT peptide infusion over 2 hours daily LSALT peptide: 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.

Units	Counts
Participants	OG000

Secondary

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

A comparison of change from baseline in SOFA score. A negative value indicates a decrease in SOFA score compared to the baseline.

Posted

Mean

Full Range

score on a scale

28 days

ID	Title	Description
OG000	Placebo	100 mL drug-free IV saline infusion over 2 hours daily Placebo: 0.9% saline solution
OG001	LSALT	100 mL of 5 mg IV LSALT peptide infusion over 2 hours daily LSALT peptide: 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.

Units	Counts
Participants

Secondary

Change in Liver Function by Alanine Aminotransferase (ALT) Test

ALT measured in IU/L

Change from baseline liver function by ALT.

Posted

Mean

95% Confidence Interval

IU/L

28 days

ID	Title	Description
OG000	Placebo	100 mL drug-free IV saline infusion over 2 hours daily Placebo: 0.9% saline solution
OG001	LSALT	100 mL of 5 mg IV LSALT peptide infusion over 2 hours daily LSALT peptide: 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.

Units	Counts
Participants	OG000

Secondary

Change in Liver Function by Aspartate Transferase (AST) Test

AST measured in IU/L

Change from baseline in liver function by AST.

Posted

Mean

95% Confidence Interval

IU/L

28 days

ID	Title	Description
OG000	Placebo	100 mL drug-free IV saline infusion over 2 hours daily Placebo: 0.9% saline solution
OG001	LSALT	100 mL of 5 mg IV LSALT peptide infusion over 2 hours daily LSALT peptide: 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.

Units	Counts
Participants	OG000

Secondary

Change in Liver Function by Total Bilirubin Test

Total bilirubin measured in umol/L

Change from baseline in liver function by bilirubin.

Posted

Mean

Standard Deviation

umol/L

28 days

ID	Title	Description
OG000	Placebo	100 mL drug-free IV saline infusion over 2 hours daily Placebo: 0.9% saline solution
OG001	LSALT	100 mL of 5 mg IV LSALT peptide infusion over 2 hours daily LSALT peptide: 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.

Units	Counts
Participants	OG000

Secondary

Change in Renal Function by Serum Creatinine (SCr) Test

SCr measured in umol/L

Change in serum creatinine from baseline at day 28 (EOS)

Posted

Mean

Standard Deviation

umol/L

28 days

ID	Title	Description
OG000	Placebo	100 mL drug-free IV saline infusion over 2 hours daily Placebo: 0.9% saline solution
OG001	LSALT	100 mL of 5 mg IV LSALT peptide infusion over 2 hours daily LSALT peptide: 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.

Units	Counts
Participants	OG000

Secondary

Change in Activated Coagulation Time (ACT)

ACT measured in seconds

Change from baseline to day 28 (EOS) in prothrombin time (PT).

Posted

Mean

Standard Deviation

sec

28 days

ID	Title	Description
OG000	Placebo	100 mL drug-free IV saline infusion over 2 hours daily Placebo: 0.9% saline solution
OG001	LSALT	100 mL of 5 mg IV LSALT peptide infusion over 2 hours daily LSALT peptide: 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.

Units	Counts
Participants	OG000

Secondary

Change in Activated Partial Thromboplastin Time (aPTT)

aPTT measured in seconds

Change from baseline to day 28 (EOS) in aPTT.

Posted

Mean

Standard Deviation

sec

28 days

ID	Title	Description
OG000	Placebo	100 mL drug-free IV saline infusion over 2 hours daily Placebo: 0.9% saline solution
OG001	LSALT	100 mL of 5 mg IV LSALT peptide infusion over 2 hours daily LSALT peptide: 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.

Units	Counts
Participants	OG000

Secondary

Change in Prothrombin International Normalized Ratio (INR)

Change from baseline to day 28 (EOS) in prothrombin INR.

Posted

Mean

Standard Deviation

ratio

28 days

ID	Title	Description
OG000	Placebo	100 mL drug-free IV saline infusion over 2 hours daily Placebo: 0.9% saline solution
OG001	LSALT	100 mL of 5 mg IV LSALT peptide infusion over 2 hours daily LSALT peptide: 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.

Units	Counts
Participants	OG000

Secondary

Vasopressor-free Days

The data are not reported because testing for this specific measure was not run as the clinical sites did not have the ability/means to perform the assessment. Additionally, there are no plans to collect or analyze the data in the future.

Posted

28 days

ID	Title	Description
OG000	Placebo	100 mL drug-free IV saline infusion over 2 hours daily Placebo: 0.9% saline solution
OG001	LSALT	100 mL of 5 mg IV LSALT peptide infusion over 2 hours daily LSALT peptide: 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.

Units	Counts
Participants	OG000

Secondary

Change From Maximal Radiographic Damage to EOT

Posted

28 days

ID	Title	Description
OG000	Placebo	100 mL drug-free IV saline infusion over 2 hours daily Placebo: 0.9% saline solution
OG001	LSALT	100 mL of 5 mg IV LSALT peptide infusion over 2 hours daily LSALT peptide: 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.

Units	Counts
Participants	OG000

Secondary

Change in Renal Function by Estimated Glomerular Filtration Rate (eGFR) Test

eGFR measured in ml/min/1.73m2

Posted

28 days

ID	Title	Description
OG000	Placebo	100 mL drug-free IV saline infusion over 2 hours daily Placebo: 0.9% saline solution
OG001	LSALT	100 mL of 5 mg IV LSALT peptide infusion over 2 hours daily LSALT peptide: 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.

Units	Counts
Participants

Secondary

Change in Hs-troponin Levels

Posted

28 days

ID	Title	Description
OG000	Placebo	100 mL drug-free IV saline infusion over 2 hours daily Placebo: 0.9% saline solution
OG001	LSALT	100 mL of 5 mg IV LSALT peptide infusion over 2 hours daily LSALT peptide: 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.

Units	Counts
Participants	OG000

Secondary

Change in Antiviral IgG, IgA, and IgM Levels

Immunoglobulins measured in mg/dL

Posted

28 days

ID	Title	Description
OG000	Placebo	100 mL drug-free IV saline infusion over 2 hours daily Placebo: 0.9% saline solution
OG001	LSALT	100 mL of 5 mg IV LSALT peptide infusion over 2 hours daily LSALT peptide: 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.

Units	Counts
Participants	OG000

Other Pre-specified

Health Outcomes Endpoint: Total Healthcare Costs From Admission to Discharge Between Treatment Groups

Healthcare costs were not analyzed in this study.

Posted

28 days

ID	Title	Description
OG000	Placebo	100 mL drug-free IV saline infusion over 2 hours daily Placebo: 0.9% saline solution
OG001	LSALT	100 mL of 5 mg IV LSALT peptide infusion over 2 hours daily LSALT peptide: 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.

Units	Counts
Participants	OG000

Other Pre-specified

Exploratory Endpoint: Change in Serum Cytokines Including IL-1a, IL-1b, and Ferritin Levels as Well as Other Exploratory Biomarkers Drawn at the Same Time as LSALT Peptide Concentrations

Fold change from baseline cytokines measured in ng/mL

Fold change in serum cytokine levels from baseline to day 28 (EOT).

Posted

Median

Inter-Quartile Range

foldchange

28 days

ID	Title	Description
OG000	Placebo	100 mL drug-free IV saline infusion over 2 hours daily Placebo: 0.9% saline solution
OG001	LSALT	100 mL of 5 mg IV LSALT peptide infusion over 2 hours daily LSALT peptide: 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.

Units	Counts
Participants

Other Pre-specified

Exploratory Endpoint: Change in Baseline Antiviral Immunoglobulins (IgG, IgM, IgA) at EOS

Immunoglobulins measured in mg/dL

Change in baseline antiviral immunoglobulins were not analyzed in this study.

Posted

28 days

ID	Title	Description
OG000	Placebo	100 mL drug-free IV saline infusion over 2 hours daily Placebo: 0.9% saline solution
OG001	LSALT	100 mL of 5 mg IV LSALT peptide infusion over 2 hours daily LSALT peptide: 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.

Units	Counts
Participants	OG000

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	100 mL drug-free IV saline infusion over 2 hours daily Placebo: 0.9% saline solution	0	31	8	31	22	31
EG001	LSALT	100 mL of 5 mg IV LSALT peptide infusion over 2 hours daily LSALT peptide: 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.	1	30	10	30	14	30

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA v.23.0	Systematic Assessment	EG0001 affected31 at risk EG0011 affected30 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA v.23.0	Systematic Assessment	EG0001 affected31 at risk EG0010 affected30 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA v.23.0	Systematic Assessment	EG0001 affected31 at risk EG0010 affected30 at risk
Acute respiratory distress syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA v.23.0	Systematic Assessment	EG0001 affected31 at risk EG0012 affected30 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA v.23.0	Systematic Assessment	EG0001 affected31 at risk EG0010 affected30 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA v.23.0	Systematic Assessment	EG0001 affected31 at risk EG0010 affected30 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA v.23.0	Systematic Assessment	EG0001 affected31 at risk EG0010 affected30 at risk
Sinus arrest	Cardiac disorders	MedDRA v.23.0	Systematic Assessment	EG0001 affected31 at risk EG0010 affected30 at risk
Sinus bradycardia	Cardiac disorders	MedDRA v.23.0	Systematic Assessment	EG0001 affected31 at risk EG0010 affected30 at risk
Bacterial sepsis	Infections and infestations	MedDRA v.23.0	Systematic Assessment	EG0002 affected31 at risk EG0010 affected30 at risk
Embolism	Vascular disorders	MedDRA v.23.0	Systematic Assessment	EG0001 affected31 at risk EG0010 affected30 at risk
Hypotension	Vascular disorders	MedDRA v.23.0	Systematic Assessment	EG0001 affected31 at risk EG0011 affected30 at risk
Cytokine release syndrome	Immune system disorders	MedDRA v.23.0	Systematic Assessment	EG0001 affected31 at risk EG0010 affected30 at risk
Blood glucose increase	Investigations	MedDRA v.23.0	Systematic Assessment	EG0001 affected31 at risk EG0010 affected30 at risk
Delirium	Psychiatric disorders	MedDRA v.23.0	Systematic Assessment	EG0001 affected31 at risk EG0010 affected30 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA v.23.0	Systematic Assessment	EG0000 affected31 at risk EG0011 affected30 at risk
Alkalosis	Metabolism and nutrition disorders	MedDRA v.23.0	Systematic Assessment	EG0000 affected31 at risk EG0010 affected30 at risk
Hypertension	Vascular disorders	MedDRA v.23.0	Systematic Assessment	EG0000 affected31 at risk EG0011 affected30 at risk
Atrial tachycardia	Cardiac disorders	MedDRA v.23.0	Systematic Assessment	EG0000 affected31 at risk EG0011 affected30 at risk
Multiple organ dysfunction syndrome	General disorders	MedDRA v.23.0	Systematic Assessment	EG0000 affected31 at risk EG0011 affected30 at risk
Septic shock	Infections and infestations	MedDRA v.23.0	Systematic Assessment	EG0000 affected31 at risk EG0011 affected30 at risk
Superinfection	Infections and infestations	MedDRA v.23.0	Systematic Assessment	EG0000 affected31 at risk EG0011 affected30 at risk
Alanine aminotransferase increase	Investigations	MedDRA v.23.0	Systematic Assessment	EG0000 affected31 at risk EG0011 affected30 at risk
Aspartate aminotransferase increase	Investigations	MedDRA v.23.0	Systematic Assessment	EG0000 affected31 at risk EG0011 affected30 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA v.23.0	Systematic Assessment	EG0000 affected31 at risk EG0011 affected30 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA v.23.0	Systematic Assessment	EG0000 affected31 at risk EG0011 affected30 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Alanine aminotransferase increase	Investigations	MedDRA v.23.0	Systematic Assessment	EG0009 affected31 at risk EG0015 affected30 at risk
Aspartate aminotransferase increase	Investigations	MedDRA v.23.0	Systematic Assessment	EG0003 affected31 at risk EG0012 affected30 at risk
Gamma-glutamyltransferase increase	Investigations	MedDRA v.23.0	Systematic Assessment	EG0002 affected31 at risk EG0010 affected30 at risk
Constipation	Gastrointestinal disorders	MedDRA v.23.0	Systematic Assessment	EG0003 affected31 at risk EG0012 affected30 at risk
Toothache	Gastrointestinal disorders	MedDRA v.23.0	Systematic Assessment	EG0002 affected31 at risk EG0010 affected30 at risk
Tachypnoea	Respiratory, thoracic and mediastinal disorders	MedDRA v.23.0	Systematic Assessment	EG0002 affected31 at risk EG0010 affected30 at risk
Bradycardia	Cardiac disorders	MedDRA v.23.0	Systematic Assessment	EG0002 affected31 at risk EG0010 affected30 at risk
Pyrexia	General disorders	MedDRA v.23.0	Systematic Assessment	EG0002 affected31 at risk EG0010 affected30 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA v.23.0	Systematic Assessment	EG0002 affected31 at risk EG0011 affected30 at risk
Anxiety	Psychiatric disorders	MedDRA v.23.0	Systematic Assessment	EG0002 affected31 at risk EG0010 affected30 at risk
Confusional state	Psychiatric disorders	MedDRA v.23.0	Systematic Assessment	EG0002 affected31 at risk EG0010 affected30 at risk
Hypertension	Vascular disorders	MedDRA v.23.0	Systematic Assessment	EG0003 affected31 at risk EG0010 affected30 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA v.23.0	Systematic Assessment	EG0000 affected31 at risk EG0012 affected30 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA v.23.0	Systematic Assessment	EG0000 affected31 at risk EG0012 affected30 at risk

First MCP Posted Date

ID	Term
D045169	Severe Acute Respiratory Syndrome
D058186	Acute Kidney Injury
D012128	Respiratory Distress Syndrome

Ancestor Terms

ID	Term
D012141	Respiratory Tract Infections
D007239	Infections
D018352	Coronavirus Infections
D003333	Coronaviridae Infections
D030341	Nidovirales Infections
D012327	RNA Virus Infections
D014777	Virus Diseases
D012140	Respiratory Tract Diseases
D051437	Renal Insufficiency
D007674	Kidney Diseases
D014570	Urologic Diseases
D052776	Female Urogenital Diseases
D005261	Female Urogenital Diseases and Pregnancy Complications
D000091642	Urogenital Diseases
D052801	Male Urogenital Diseases
D008171	Lung Diseases
D012120	Respiration Disorders