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). (VANGARD)

PhaseBio Pharmaceuticals

Status and phase: Terminated; Phase 2

Conditions: Hypoxic Respiratory Failure; Respiratory Failure; Respiratory Insufficiency; Respiratory Complication; Cytokine Storm; Acute Respiratory Distress Syndrome; SARS-CoV-2; Pulmonary Inflammation; Pulmonary Edema; Cardiac Event; Coronavirus; Cardiac Dysfunction; Cardiac Infarct; Cardiac Failure; Hypoxemic Respiratory Failure; Cardiac Complication; Pneumonia; COVID 19

Treatments: Drug: Pemziviptadil (PB1046); Drug: Low Dose (10 mg) Control

Study type: Interventional

Funder types: Industry

Identifiers

NCT04433546

PB1046-PT-CL-0007

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 54 patients

Sex: All

Ages: 18 to 85 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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54 participants in 3 patient groups, including a placebo group

High Dose (100 mg) Group

Experimental group

Description:

High: Pemziviptadil (PB1046) 100 mg subcutaneous (SC) weekly for 4 weeks or until hospital discharge

Treatment:

Drug: Pemziviptadil (PB1046)

Middle Dose (40 mg) Group

Experimental group

Description:

Middle: Pemziviptadil (PB1046) 40 mg SC weekly for 4 weeks or until hospital discharge

Treatment:

Drug: Pemziviptadil (PB1046)

Low Dose (10 mg) Control Group

Placebo Comparator group

Description:

Low Control: Pemziviptadil (PB1046) 10 mg SC weekly for 4 weeks or until hospital discharge

Treatment:

Drug: Low Dose (10 mg) Control