LSALT Peptide vs. Placebo to Prevent ARDS and Acute Kidney Injury in Patients Infected With SARS-CoV-2 (COVID-19)
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|ClinicalTrials.gov Identifier: NCT04402957|
Recruitment Status : Not yet recruiting
First Posted : May 27, 2020
Last Update Posted : June 16, 2020
|Condition or disease||Intervention/treatment||Phase|
|COVID Severe Acute Respiratory Syndrome Sars-CoV2 Acute Kidney Injury||Drug: LSALT peptide Drug: Placebo||Phase 2|
This is a global, multicenter, randomized, double-blind, placebo-controlled, proof of concept study of LSALT peptide as prevention of acute respiratory distress syndrome (ARDS) and acute kidney injury in patients infected with SARS-CoV-2 (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. Patients and, if necessary, the Legal Authorized Representative (LAR), the Investigational Staff, and the Sponsor and its representatives will not know the randomization schemata. The Pharmacist at the site will be unblinded and prepare drug/placebo for injection.
The study will have staggered enrolment in that a cohort of 6 patients will be enrolled into the study during the first wave. Further cohorts of 6 patients will be enrolled only after the Data and Safety Monitoring Board (DSMB; refer to the DSMB Charter) has assessed the adequacy of treatment based upon clinical data of the patient, target drug concentrations, and data obtained from the AB001 PK study in healthy subjects to offer recommendations to the Sponsor. In the absence of adverse events or any safety issues during the course of study, the DSMB may recommend additional cohorts of 6 patients to be studied as planned in this protocol. At no time will patients be dosed for more than 14 days of therapy. The DSMB Charter will outline all processes for changes to the protocol and protocol design prior to the first patient being enrolled into study.
Patients will be physically examined throughout the study period, including respiratory assessments. Vital signs, adverse events (AE), routine blood chemistries, coagulation, hematology, and urinalysis will be assessed throughout the study. LSALT peptide and metabolite concentrations and cytokine levels will be assessed daily at the mid-point (1 hour) and immediately at the end of the 2-hour study drug infusion. An ECG will be recorded at Baseline prior to drug therapy, Day 3, and at EOS. A chest x-ray will be obtained at Baseline and Day 3 as well as at time of clinical improvement, EOT, and EOS. Questionnaires (APACHE II, Berlin Definition, SOFA, and modified Medical Research Council Dyspnea Scale) will be assessed each morning and when indicated by the PI.
Duration of therapy will be a maximum of 14 days. Patients will be maintained on the standard of care for the treatment of COVID-19 as defined by the institutional guidelines. Co-morbidities and concomitant medications will be reviewed daily and documented in the patient's eCRF. The risk of venous thromboembolism (VTE), a potential consequence of SARS-CoV-2 infection, will be assessed daily and prophylaxis will be included as standard of care for every patient. Please refer to antithrombotic therapy in patients with COVID-19 (COVID-19 Treatment Guidelines Panel, 12-May-2020).
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||60 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Multicenter, Randomized, Double-Blind, Placebo-Controlled, Proof of Concept Study of LSALT Peptide as Prevention of Acute Respiratory Distress Syndrome (ARDS) and Acute Kidney Injury in Patients Infected With SARS-CoV-2 (COVID-19)|
|Estimated Study Start Date :||July 1, 2020|
|Estimated Primary Completion Date :||December 31, 2020|
|Estimated Study Completion Date :||June 30, 2021|
Placebo Comparator: Placebo
100 mL drug-free IV saline infusion over 2 hours daily
0.9% saline solution
100 mL of 5 mg IV LSALT peptide infusion over 2 hours daily
Drug: 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, potentially minimizing off-target or other adverse effects. 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. DPEP-1 represents a new molecular pathway for leukocyte adhesion discovered by Arch Biopartners scientists.
Other Name: Metablok
- Development of Acute Respiratory Distress Syndrome (ARDS) and Other Organ Injuries [ Time Frame: 28 days ]To evaluate the efficacy of intravenous LSALT peptide plus standard of care to prevent the progression of COVID-19 to mild, moderate or severe ARDS, acute kidney injury, cardiomyopathy, acute liver injury, coagulopathy, or death in patients infected with SARS-CoV-2 compared with placebo plus standard of care.
- Ventilation-free days [ Time Frame: 28 days ]High-frequency oscillatory ventilation, with its rapid delivery of low tidal volumes and a respiratory rate in the range of 60 to 900 breaths/minute, has also been utilized in ARDS patients.
- Time on nasal cannula or oxygen masks [ Time Frame: 28 days ]Oxygen therapy provided as non-invasive therapy for ARDS patients.
- 28 day mortality - all cause and attributable [ Time Frame: 28 days ]28 day mortality - all cause and attributable
- ICU and hospitalization length of stay (days) [ Time Frame: 28 days ]ICU and hospitalization length of stay (days)
- SARS-CoV2 testing [ Time Frame: 28 days ]Swab (nasopharyngeal, nasal, throat, sputum, or lower respiratory tract) at baseline (Day 1) and every 3 days thereafter until eradication → virologic clearance rate
- Need and duration for extracorporeal membrane oxygenation (ECMO) [ Time Frame: 28 days ]Extracorporeal membrane oxygenation (ECMO) is often used for severe ARDS to allow lung healing/repair and reverse respiratory failure.
- Vasopressor free days [ Time Frame: 28 days ]Vasopressor free days
- Radiographic pulmonary assessments [ Time Frame: 28 days ]Chest X-rays performed at Baseline, Day 3, at clinical improvement, and end-of-treatment (EOT) and study (EOS) to determine presence of bilateral opacities.
- Change in modified Medical Research Council (mMRC) dyspnea and Sequential Organ Failure Assessment (SOFA) scores [ Time Frame: 28 days ]Change in daily mMRC dyspnea and SOFA scores (0 to 4) with 4 being the most severe outcome
- Incidence of non-lung disorders [ Time Frame: 28 days ]Incidence of other organ (non-lung) disorders
- Measures of liver dysfunction [ Time Frame: 28 days ]Change in liver function tests (ALT, AST, and total bilirubin levels) from baseline
- Measures of kidney dysfunction [ Time Frame: 28 days ]Change in SCr and eGFR from baseline
- Measures of cardiac dysfunction [ Time Frame: 28 days ]Change in highly-sensitive troponin (hs-troponin) from baseline
- Measures of coagulopathies [ Time Frame: 28 days ]Change from baseline ACT, aPTT, and/or PT/INR levels
- Changes in immunogenic responses [ Time Frame: 28 days ]Change in baseline antiviral immunoglobulins (IgG, IgM) at EOS.
- Healthcare outcomes [ Time Frame: 28 days ]Changes in total healthcare costs from admission to discharge between treatment groups.
- Molecular changes in pro-inflammatory pathways [ Time Frame: 28 days ]Change in serum cytokines including IL-1α, IL-1ß, IL-1ra, IL-5, IL-6, IL-8, IL-12, TNFα, CXCL10/IP10, MCP-3, and ferritin drawn at the same time as LSALT peptide levels
- Pharmacokinetics of LSALT peptide [ Time Frame: 28 days ]Pharmacokinetics of LSALT peptide over the study period.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04402957
|Contact: Daniel A Muruve, MDfirstname.lastname@example.org|
|Contact: Richard Muruveemail@example.com|