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).

Phase 2TerminatedNCT04433546

PhaseBio Pharmaceuticals Inc.54 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Acute Respiratory Distress Syndrome

Eligibility

Sex: ALLMin age: 18 YearsMax age: 85 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Time to clinical recovery from initiation of pemziviptadil (PB1046)

Time frame: 28 days

Secondary Outcomes

Time to clinical recovery (being well enough for hospital discharge or returning to normal baseline activity level prior to discharge)

Time frame: 28 days

Time to hospital discharge

Time frame: Any time point between injection initiation and Day 28

All-cause mortality

Time frame: 28 days

Reduction in hospital resource utilization defined as a composite of: total days: in hospital, in ICU, on ventilator, on ECMO, with invasive hemodynamic monitoring, with mechanical circulatory support, and with inotropic or vasopressor therapy

Composite of: Total hospital days, Total ICU days, Total days of ventilator use, Total days of ECMO, Total days of invasive hemodynamic monitoring, Total days of mechanical circulatory support, Total days of inotropic or vasopressor therapy

Time frame: 28 days

Time to clinical improvement as defined by reduction of at least 2 points on an 8-category ordinal scale of clinical improvement or discharge from hospital, whichever comes first.

Time frame: Any time point between injection initiation and Day 28

Change from baseline in cardiac marker troponin I (TrI)