AV-001 for Hospitalized Patients With COVID-19 Disease

Official Title

A Randomized, Double-blind, Placebo-controlled, Phase 2a Multiple Ascending Dose Study to Examine the Safety, Tolerability and Efficacy of AV-001 in Patients Hospitalized with Confirmed Severe COVID-19 Disease

Details

AV-001 is a synthetic Angiopoietin-1 (Angpt-1) mimetic that has been shown to activate the Tie2 receptor tyrosine kinase; a transmembrane protein target most highly expressed on the surface of endothelial cells in the vasculature. The Tie2/Angiopoietin signaling axis has been identified as a nonredundant gatekeeper of vascular homeostasis. In healthy individuals, Tie2 is highly activated and signals the endothelium to fortify intracellular junctions and reduce expression of adhesion molecules, which serve as leukocyte tethers upon inflammation. As such, homeostatic activation results in the promotion of barrier defense against vascular leakage.

The study population for this Phase 2a study will consist of male and non-pregnant female patients, greater than or equal to 18 years of age, hospitalized with presumed pneumonia secondary to SARS-CoV-2 or other viral or bacterial infection with acute onset to a respiratory compromise requiring supplemental oxygen therapy.

You can join if...

Inclusion Criteria:

1. Able and willing to give signed informed consent
2. Patients hospitalized with a presumed diagnosis of pneumonia of < 48 hours duration requiring supplemental oxygen therapy. Eligible patients include those hospitalized for a separate non-infectious reason who subsequently develop a presumed pneumonia;
3. Radiologic imaging (chest x-ray, CT scan, etc.) evidence of pulmonary involvement with new and persistent or progressive and persistent infiltrate, consolidation or cavitation.
4. Signs and symptoms:
   At least 1 of the following signs:
   • respiratory rate > 30 breaths/min;
   • fever (> 38.0ºC or > 100.4o F);
   • leukopenia (less than or equal to 4,000 WBC/mm3 or leukocytosis (≥ 12,000 WBC/mm3);
   • adults greater than or equal to 70 years of age; altered mental status with no other recognized cause;

AND at least 1 of the following symptoms:

1. New onset of purulent sputum or change in character of sputum or increased respiratory secretions;
2. New onset or worsening cough, or dyspnea, or tachypnea;
3. Rales or bronchial breath sounds;
4. Female patients of reproductive potential must be on an effective contraceptive method

Exclusion Criteria:

1. Pregnant and/or lactating women
2. Patients included in any other interventional trial
3. Use of endotracheal intubation and mechanical ventilation or extracorporeal membrane oxygenation (ECMO) at screening
4. Any concurrent serious medical condition or concomitant medication that would preclude participation in the study including but not limited to:
   • Septic shock as defined by systolic blood pressure (SBP) < 90 mmHg or diastolic blood pressure (DBP) of < 60 mmHg;
   • Multiple organ failure;
   • Are moribund irrespective of the provision of treatments;
   • Any significant bleeding disorder or vasculitis;
   • Any serious, nonhealing wound, peptic ulcer or bone fracture;
   • Liver cirrhosis;
   • History of a hypertensive crisis or hypertensive encephalopathy, or current, poorly controlled hypertension or hypotension;
   • Severe renal insufficiency or end stage renal disease as determined by estimated glomerular filtration rate <30mL/min/1.73m2;
   • ARDS risk factors of aspiration pneumonia, non-cardiac shock, trauma, blood transfusion or drug overdose.
5. Any thromboembolic event within the past 3 months;
6. Symptomatic congestive heart failure or symptomatic or poorly controlled cardiac arrhythmia > class II as per New York Heart Association (NYHA) classification;
7. History of autonomic disorders or uncontrolled hypotension
8. Hypersensitivity to drug products containing polyethylene glycol (PEG)
9. Any other condition which the Principal Investigator feels may jeopardize the safety of the patient or the objectives of the study.