Pemziviptadil (PB1046), a Long-acting, Sustained Release Human VIP Analogue, Intended to Provide Clinical Improvement to Hospitalized COVID-19 Patients at High Risk for Rapid Clinical Deterioration and Acute Respiratory Distress Syndrome (ARDS).
Pemziviptadil (PB1046), a Long-acting, Sustained Release Human VIP Analogue, Intended to Provide Clinical Improvement to Hospitalized COVID-19 Patients at High Risk for Rapid Clinical Deterioration and Acute Respiratory Distress Syndrome (ARDS).
This is a multicenter, randomized, double-blind, parallel group study to investigate the
 efficacy of pemziviptadil (PB1046) by improving the clinical outcomes in hospitalized
 COVID-19 patients at high risk for rapid clinical deterioration, acute respiratory distress
 syndrome (ARDS) and death.

 The study will enroll approximately 210 hospitalized COVID-19 patients who require urgent
 decision-making and treatment at approximately 20 centers in the United States.
The study will consist of a Screening/Pre-treatment period, on-site randomization to study
 treatment. On Day 0 (Visit 2) subjects who meet inclusion criteria and none of exclusion
 criteria will receive a weekly subcutaneous injection that will continue once weekly until
 hospital discharge or for a maximum of 4 weeks during hospitalization, whichever is shorter.

 All subjects will be randomized to either a low control (10 mg), middle (40 mg), or high (100
 mg) dose of active treatment. If subject is not discharged, they will continue to Day 7, 14,
 21 treatments. Pemziviptadil (PB1046) is expected to improve the clinical outcomes of
 hospitalized COVID-19 subjects with an earlier hospital discharge and improvement in
 survival.

 The duration of hospitalization for each subject will be determined by clinical status
 independent of study procedures. The estimated duration of the study for each subject,
 including screening, is approximately 35+7 days. The subjects may be involved up to 42 days.
Inclusion Criteria:

 1. Written or witnessed verbal informed consent from patient or remote legal authorized
 representative (LAR) or remote family member as permitted by governing local or
 central Institutional Review Board (IRB)/independent Ethic Committee (IEC).

 2. Male or female 18-85 years old hospitalized COVID-19 patients (positive local
 SARS-CoV2 test)

 3. Receiving oxygen (O2) by face mask or nasal cannula/prongs and/or with elevated
 markers of cardiac injury or dysfunction (hsTnI or NT-proBNP) as assessed by local
 testing

 Exclusion Criteria:

 Subjects will be excluded from the study if they meet any of the following criteria:

 1. Patients considered unsalvageable or expected to expire within 24 hours

 2. On mechanical ventilation or imminent need for mechanical ventilation expected in the
 next 24 hours

 3. Evidence of acute end-organ injury in 2 or more organ systems (not including cardiac
 or pulmonary), such as, renal, hepatic, or CNS injury

 4. Receiving another investigational therapy for treatment or prevention of
 COVID-19-related hypoxemic respiratory failure or ARDS other than antiviral therapy

 5. Systolic blood pressure (SBP) < 95 mmHg and/or diastolic blood pressure (DBP) < 50
 mmHg or overt symptomatic hypotension during screening

 6. Resting heart rate > 110 BPM (beats per minute) during screening

 7. Severe chronic renal failure as measured by the estimated glomerular filtration rate
 (eGFR) of < 30 mL/min/1.73m2 using the local laboratory calculation of eGFR.

 8. Significant liver dysfunction as measured by any one of the following at screening:

 -  ALT (Alanine transaminase) > 3.0 times ULN (upper limit of normal)

 -  AST (Aspartate transaminase) > 3.0 times ULN

 -  Serum bilirubin ≥ 1.6 mg/dL

 9. Any in-patient surgical procedure or hospitalization (defined as > 23 hours) within 30
 days of subject screening except for prior hospitalization for COVID-19

 10. Known hypersensitivity to study drug or any of the excipients of the drug formulation

 11. Pregnant or lactating female subjects

 12. Any other condition which, in the opinion of the Investigator, would place the subject
 at increased risk or would preclude obtaining informed consent or confound the
 objectives of study