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).

Pneumonia Clinical Trial

— VANGARD  

Official title:

A Randomized, Double-Blind, Parallel Group Study to Assess the Efficacy and Safety of Once Weekly Subcutaneous Injections of Pemziviptadil (PB1046), a Sustained-Release VIP (Vasoactive Intestinal Peptide) ANalogue, in Hospitalized COVID-19 Patients at HiGh Risk for Rapid Clinical Deterioration and ARDS (PB1046 VANGARD Study)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04433546
• Other study ID #: PB1046-PT-CL-0007
• Status: Terminated
• Phase: Phase 2
• Start date: July 15, 2020
• Est. completion date: December 2, 2020

Study information

• Verified date: December 2020
• Source: PhaseBio Pharmaceuticals Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 54
• Est. completion date: December 2, 2020
• Est. primary completion date: December 2, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Lung Injury
• Acute Respiratory Distress Syndrome
• Cardiac Complication
• Cardiac Dysfunction
• Cardiac Event
• Cardiac Failure
• Cardiac Infarct
• Clinical Deterioration
• Coronavirus
• COVID 19
• Cytokine Storm
• Heart Failure
• Hypoxemic Respiratory Failure
• Hypoxic Respiratory Failure
• Inflammation
• Pneumonia
• Pulmonary Edema
• Pulmonary Inflammation
• Pulmonary Valve Insufficiency
• Respiratory Complication
• Respiratory Distress Syndrome, Adult
• Respiratory Distress Syndrome, Newborn
• Respiratory Failure
• Respiratory Insufficiency
• SARS-CoV-2
• Syndrome

Intervention

Drug:
• Pemziviptadil (PB1046)
Pemziviptadil (PB1046), Once Weekly Subcutaneous Injection
• Low Dose (10 mg) Control
Pemziviptadil (PB1046), Once Weekly Subcutaneous Injection (10 mg diluted in sodium chloride to match active drug volume)

Locations

Country	Name	City	State
United States	Baptist Health Research Institute	Jacksonville	Florida
United States	The University of Kansas Medical Center	Kansas City	Kansas
United States	Sarasota Memorial Hospital	Sarasota	Florida
United States	Adventist Healthcare White Oak Medical Center	Silver Spring	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
PhaseBio Pharmaceuticals Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Impact on invasive hemodynamic parameters as measured by pulmonary artery pressure if patients require right-heart catherization		Any time point between injection initiation and Day 35+7
Other	Impact on invasive hemodynamic parameters as measured by cardiac output if patients require right-heart catherization		Any time point between injection initiation and Day 35+7
Other	Incidence of multi-system organ failure (MSOF)		Any time point between injection initiation and Day 35+7
Other	Number of multi-system organ failure (MSOF) free days		Any time point between injection initiation and Day 35+7
Other	Number of subjects requiring extracorporeal membrane oxygenation (ECMO)		Any time point between injection initiation and Day 35+7
Other	Change in circulating ferritin		Any time point between injection initiation and Day 35+7
Other	Change in circulating D-dimer		Any time point between injection initiation and Day 35+7
Other	Change in liver function		Any time point between injection initiation and Day 35+7
Other	Change in other blood chemistry		Any time point between injection initiation and Day 35+7
Other	Change in hematology		Any time point between injection initiation and Day 35+7
Other	Change in inflammatory markers		Any time point between injection initiation and Day 35+7
Other	Change in coagulation markers		Any time point between injection initiation and Day 35+7
Other	Percent of clinical failure		Any time point between injection initiation and Day 35+7
Primary	Time to clinical recovery from initiation of pemziviptadil (PB1046)		28 days
Secondary	Time to clinical recovery (being well enough for hospital discharge or returning to normal baseline activity level prior to discharge)		28 days
Secondary	Time to hospital discharge		Any time point between injection initiation and Day 28
Secondary	All-cause mortality		28 days
Secondary	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	28 days
Secondary	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.		Any time point between injection initiation and Day 28
Secondary	Change from baseline in cardiac marker troponin I (TrI)		Any time point between injection initiation and Day 35+7
Secondary	Change from baseline in cardiac marker NT-proBNP/BNP		Any time point between injection initiation and Day 35+7
Secondary	Change from baseline in TNF alpha		Any time point between injection initiation and Day 35+7
Secondary	Change from baseline in IL-1		Any time point between injection initiation and Day 35+7
Secondary	Change from baseline in IL-6		Any time point between injection initiation and Day 35+7
Secondary	Incidence and severity of any treatment emergent adverse events (TEAEs) or serious adverse events (SAEs) as determined by clinical adverse events (AEs) and their relationship to pemziviptadil (PB1046).		Any time point between injection initiation and Day 35+7
Secondary	Incidence and severity of any treatment emergent adverse events (TEAEs) or serious adverse events (SAEs) as determined by vital signs and their relationship to pemziviptadil (PB1046)		Any time point between injection initiation and Day 35+7
Secondary	Incidence and severity of any treatment emergent adverse events (TEAEs) or serious adverse events (SAEs) as determined by laboratory results and their relationship to pemziviptadil (PB1046)		Any time point between injection initiation and Day 35+7
Secondary	Incidence and severity of any treatment emergent adverse events (TEAEs) or serious adverse events (SAEs) as determined by electrocardiogram (ECG) abnormalities and their relationship to pemziviptadil (PB1046)		Any time point between injection initiation and Day 35+7
Secondary	Incidence and severity of any treatment emergent adverse events (TEAEs) or serious adverse events (SAEs) as determined by incidence of anti-drug antibodies and their relationship to pemziviptadil (PB1046)		Any time point between injection initiation and Day 35+7