A Phase 2a Multiple Ascending Dose Study to Examine the Safety, Tolerability and Efficacy of AV-001 Injection in Patients with Pneumonia Due To COVID-19 or Respiratory Infections.

The purpose of this research study is to assess the safety, tolerability (primary objective),  efficacy, and target engagement (secondary objective) of multiple IV administrations of AV-001 Injection compared with placebo in patients with pneumonia due to COVID-19 or other viral/bacterial respiratory infections.  In addition, patients on both treatment arms will receive supportive care (standard of care * SOC) according to the SOC for the trial site hospital. The placebo looks like active drug but does not contain active drug. 

Inclusion criteria

1. Aged ≥18 years at the time of screening.

2. Are able and willing to give signed informed consent (legally authorized representative can provide informed consent if needed).

3. Patients hospitalized with a presumed diagnosis of pneumonia of 30 breaths/min; o fever (> 38.0ºC or > 100.4o F); o leukopenia (≤ 4,000 WBC/mm3 or leukocytosis (≥ 12,000 WBC/mm3); o adults ≥ 70 years of age; altered mental status with no other recognized cause;

And at least 1 of the following symptoms:

o New onset of purulent sputum or change in character of sputum or increased respiratory secretions;

o New onset or worsening cough, or dyspnea, or tachypnea;

o Rales or bronchial breath sounds;

1. Female patients of reproductive potential must be on an effective contraceptive method. Women will be considered to be of reproductive potential unless they have been surgically sterilized (by hysterectomy and/or bilateral oophorectomy and/or bilateral salpingectomy or tubal ligation) or are post-menopausal (age-appropriate spontaneous amenorrhea for ≥ 12 months in the absence of oral contraceptive use for > 12 months); Exclusion criteria

2. Pregnant and/or lactating women; 2. Patients included in any other interventional trial (patients taking part in observational trials may be enrolled if the total blood volume to be drawn across both studies and for therapeutic purposes is not anticipated to exceed 251 mL over any 8-week period per patient for DL1, DL2 and DL3 and 227 mL over any 8-week period per patient for DL4);

3. Use of endotracheal intubation and mechanical ventilation or extracorporeal membrane oxygenation (ECMO) at time of study screening;

4. Any concurrent serious medical condition that would preclude participation in the study including but not limited to: o Septic shock as defined by systolic blood pressure (SBP) < 90 mmHg or diastolic blood pressure (DBP) of < 60 mmHg; o Multiple organ failure; o Are moribund irrespective of the provision of treatments; o Any significant bleeding disorder or vasculitis; o Any serious, nonhealing wound, peptic ulcer or bone fracture; o Liver cirrhosis; o History of a hypertensive crisis or hypertensive encephalopathy, or current, poorly controlled hypertension or hypotension; o Severe renal insufficiency or end stage renal disease as determined by estimated glomerular filtration rate class II as per New York Heart Association (NYHA) classification;

5. History of autonomic disorders or uncontrolled hypotension;

6. Hypersensitivity to drug products containing polyethylene glycol (PEG);

7. Any other condition which the Principal Investigator feels may jeopardize the safety of the patient or the objectives of the study. The Principal Investigator should make this determination in consideration of the patient’s medical history and current clinical condition.