| Eligibility |
Inclusion Criteria
Patients who meet all of the following criteria will be eligible to participate in the
study:
1. Age =18 years;
2. Must have laboratory confirmed COVID-19;
3. Must have moderate or severe, immediately life-threatening COVID-19 or Influenza (A or
B), as follows:
a. COVID-19 patients with ARDS (Berlin Criteria) as demonstrated by:
i. Chest radiograph or CT scan showing bilateral opacities not fully explained by
effusions, lobar/lung collapse, or nodules;
ii. Respiratory failure not fully explained by cardiac failure or fluid overload; and
iii. Impaired oxygenation defined as Moderate (partial pressure of oxygen
[PaO2]:fraction of inspired oxygen [FiO2] ratio 100 mm Hg to <200 mm Hg with positive
end-expiratory airway pressure [PEEP] >5 cm H2O) or Severe (PaO2:FiO2 ratio <100 mm Hg
with PEEP>5 cm H2O) on more than 2 arterial blood gases at least 6 hours apart within
a 24 hour period;
b. Influenza (A or B) patients with ARDS (Berlin Criteria) as demonstrated by:
i. Chest radiograph or CT scan showing bilateral opacities not fully explained by
effusions, lobar/lung collapse, or nodules;
ii. Respiratory failure not fully explained by cardiac failure or fluid overload; and
iii. Impaired oxygenation defined as Severe (PaO2:FiO2 ratio<100 mm Hg with PEEP >5 cm
H2O) on more than 2 arterial blood gases at least 6 hours apart within a 24 hour
period;
4. Requires invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO)
despite standard of care rescue measures (eg, prone positioning, and/or PEEP ladder,
and/or inhaled pulmonary vasodilators, and/or recruitment maneuvers and/or
neuromuscular blockade);
5. Females of childbearing potential must have a negative serum pregnancy test at
screening;
6. Females of childbearing potential and nonsterile males must agree to use medically
effective methods of contraception from the time of informed consent through 1 month
after study drug infusion; and
7. Capable of providing informed consent, or if not capable, a legally authorized
representative is capable of providing informed consent
Exclusion Criteria
Patients who meet any of the following criteria will be excluded from participation in the
study:
1. Moribund patient who, in the opinion of the Investigator, is not expected to survive
at least 24 hours;
2. Known hypersensitivity or allergy to the study drug or any of its excipients;
3. D-dimer level >3 times above normal range;
4. Known gastric or duodenal ulcer;
5. Uncontrolled type 1 or type 2 diabetes, per judgment of the Investigator;
6. Active and untreated bacterial, fungal, parasitic, or viral infection other than
COVID-19 or Influenza (A or B). Patients with a history of a positive hepatitis B
surface antigen and/or hepatitis B core antibody must have a negative hepatitis B
polymerase chain reaction (PCR) assay result. Patients with history of a positive
hepatitis C virus antibody test must have a negative hepatitis C PCR assay result;
7. Positive testing for tuberculosis during screening;
8. Known to have received a live vaccine within the previous 1 month;
9. Immunocompromised patients, defined as those who have received a bone marrow or solid
organ transplant on immunosuppressive therapy; or history of human immunodeficiency
virus (HIV) infection who have not been taking anti retroviral therapy for at least 6
months before enrollment and/or with most recent CD4 count <200 cells/mL and/or most
recent detectable viral load within the previous 6 months;
10. Moderate to End-stage liver disease (Childs-Pugh Score >10);
11. Dialysis-dependent due to underlying chronic renal disease. Note: patients who require
dialysis for treatment of renal failure due to complications of COVID-19 or Influenza
(A or B) infection are not excluded from enrollment;
12. Significant cardiovascular disease (eg, myocardial infarction, arterial
thromboembolism, cerebrovascular thromboembolism) within 3 months prior to the start
of AVM0703 administration, including: angina requiring therapy, symptomatic peripheral
vascular disease, New York Heart Association Class III or IV congestive heart failure,
left ventricular ejection fraction <30%, left ventricular fractional shortening <20%,
or uncontrolled Grade 3 hypertension (diastolic blood pressure [DBP] >100 mm Hg or
systolic blood pressure [SBP] >150 mm Hg) despite antihypertensive therapy.
Note: patients with heart failure requiring medical support due solely to
complications of COVID-19 infection are not excluded from enrollment;
13. Significant screening 12-lead ECG abnormalities, including unstable cardiac arrhythmia
requiring medication, atrial fibrillation/flutter, left bundle-branch block, second
degree atrioventricular (AV) block type 2, third-degree AV block, Grade 2 bradycardia,
or heart rate corrected QT interval using Fridericia's formula average of triplicate
ECGs >450 ms;
14. Manic-depressive disorder, schizophrenia, or a history of severe depression or
substance abuse;
15. Pregnant or breastfeeding;
16. Concurrent enrollment in any other clinical study involving administration of a novel
(ie, unapproved or not considered standard of care) investigational pharmacological
agent(s). Concurrent enrollment in observational and device studies and studies
involving administration of pharmacological agent(s) approved for other indications or
considered emerging standard of care for treatment of COVID-19 (eg,
hydroxychloroquine, remdesivir, low-dose dexamethasone), will be allowed if approved
by the Sponsor;
17. Treatment with standard of care or off-label treatments for COVID-19 (eg, remdesivir),
not administered as part of a formal clinical study, where the first dose was
initiated within 72 hours of study drug start; and
18. Inability to obtain informed consent from the patient or legally authorized
representative.
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