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
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.
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. 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.
Other Name: Metablok
Drug: Placebo
0.9% saline solution
Inclusion Criteria (Amendment 3, 15FEB2021):
1. Male and female hospitalized patients between 18 and 80 years of age at time of
consent.
2. 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
3. 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%.
4. APACHE II score < 20 or establishment of survivability of the patient beyond 48 hours
following randomization
5. 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
6. 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.
7. 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:
1. Known sensitivity, allergy, or previous exposure to LSALT peptide.
2. Exposure to any investigational drug or device <90 days prior to entry into study.
3. 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.
4. Anticipated transfer to another hospital or medical center within 72 hours, which is
not a study site.
5. 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
6. 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.
7. As indicated in the inclusion criteria, pregnant female patients are excluded from
study. Further, female patients who are nursing are excluded from study.
8. 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.
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
Istanbul University Cerrahpasa
Istanbul, Turkey