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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)

Primary Purpose

Acute Respiratory Distress Syndrome, Coronavirus, Hypoxic Respiratory Failure

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Pemziviptadil (PB1046)
Low Dose (10 mg) Control
Sponsored by
PhaseBio Pharmaceuticals Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Respiratory Distress Syndrome focused on measuring Acute Respiratory Distress Syndrome (ARDS), Respiratory distress/failure, COVID

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Baptist Health Research Institute
  • Sarasota Memorial Hospital
  • The University of Kansas Medical Center
  • Adventist Healthcare White Oak Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

High Dose (100 mg) Group

Middle Dose (40 mg) Group

Low Dose (10 mg) Control Group

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

Time to clinical recovery from initiation of pemziviptadil (PB1046)

Secondary Outcome Measures

Time to clinical recovery (being well enough for hospital discharge or returning to normal baseline activity level prior to discharge)
Time to hospital discharge
All-cause mortality
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 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.
Change from baseline in cardiac marker troponin I (TrI)
Change from baseline in cardiac marker NT-proBNP/BNP
Change from baseline in TNF alpha
Change from baseline in IL-1
Change from baseline in IL-6
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).
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)
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)
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)
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)

Full Information

First Posted
May 28, 2020
Last Updated
December 9, 2020
Sponsor
PhaseBio Pharmaceuticals Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT04433546
Brief Title
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).
Acronym
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)
Study Type
Interventional

2. Study Status

Record Verification Date
December 2020
Overall Recruitment Status
Terminated
Why Stopped
Company no longer pursing indication
Study Start Date
July 15, 2020 (Actual)
Primary Completion Date
December 2, 2020 (Actual)
Study Completion Date
December 2, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
PhaseBio Pharmaceuticals Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Respiratory Distress Syndrome, Coronavirus, Hypoxic Respiratory Failure, Hypoxemic Respiratory Failure, Respiratory Complication, Respiratory Insufficiency, Cardiac Dysfunction, Pneumonia, Pulmonary Edema, Pulmonary Inflammation, Respiratory Failure, Cytokine Storm, COVID 19, SARS-CoV-2, Cardiac Event, Cardiac Complication, Cardiac Failure, Cardiac Infarct
Keywords
Acute Respiratory Distress Syndrome (ARDS), Respiratory distress/failure, COVID

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
54 (Actual)

8. Arms, Groups, and Interventions

Arm Title
High Dose (100 mg) Group
Arm Type
Experimental
Arm Description
High: Pemziviptadil (PB1046) 100 mg subcutaneous (SC) weekly for 4 weeks or until hospital discharge
Arm Title
Middle Dose (40 mg) Group
Arm Type
Experimental
Arm Description
Middle: Pemziviptadil (PB1046) 40 mg SC weekly for 4 weeks or until hospital discharge
Arm Title
Low Dose (10 mg) Control Group
Arm Type
Placebo Comparator
Arm Description
Low Control: Pemziviptadil (PB1046) 10 mg SC weekly for 4 weeks or until hospital discharge
Intervention Type
Drug
Intervention Name(s)
Pemziviptadil (PB1046)
Intervention Description
Pemziviptadil (PB1046), Once Weekly Subcutaneous Injection
Intervention Type
Drug
Intervention Name(s)
Low Dose (10 mg) Control
Intervention Description
Pemziviptadil (PB1046), Once Weekly Subcutaneous Injection (10 mg diluted in sodium chloride to match active drug volume)
Primary Outcome Measure Information:
Title
Time to clinical recovery from initiation of pemziviptadil (PB1046)
Time Frame
28 days
Secondary Outcome Measure Information:
Title
Time to clinical recovery (being well enough for hospital discharge or returning to normal baseline activity level prior to discharge)
Time Frame
28 days
Title
Time to hospital discharge
Time Frame
Any time point between injection initiation and Day 28
Title
All-cause mortality
Time Frame
28 days
Title
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
Description
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
Title
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
Title
Change from baseline in cardiac marker troponin I (TrI)
Time Frame
Any time point between injection initiation and Day 35+7
Title
Change from baseline in cardiac marker NT-proBNP/BNP
Time Frame
Any time point between injection initiation and Day 35+7
Title
Change from baseline in TNF alpha
Time Frame
Any time point between injection initiation and Day 35+7
Title
Change from baseline in IL-1
Time Frame
Any time point between injection initiation and Day 35+7
Title
Change from baseline in IL-6
Time Frame
Any time point between injection initiation and Day 35+7
Title
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).
Time Frame
Any time point between injection initiation and Day 35+7
Title
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)
Time Frame
Any time point between injection initiation and Day 35+7
Title
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)
Time Frame
Any time point between injection initiation and Day 35+7
Title
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)
Time Frame
Any time point between injection initiation and Day 35+7
Title
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)
Time Frame
Any time point between injection initiation and Day 35+7
Other Pre-specified Outcome Measures:
Title
Impact on invasive hemodynamic parameters as measured by pulmonary artery pressure if patients require right-heart catherization
Time Frame
Any time point between injection initiation and Day 35+7
Title
Impact on invasive hemodynamic parameters as measured by cardiac output if patients require right-heart catherization
Time Frame
Any time point between injection initiation and Day 35+7
Title
Incidence of multi-system organ failure (MSOF)
Time Frame
Any time point between injection initiation and Day 35+7
Title
Number of multi-system organ failure (MSOF) free days
Time Frame
Any time point between injection initiation and Day 35+7
Title
Number of subjects requiring extracorporeal membrane oxygenation (ECMO)
Time Frame
Any time point between injection initiation and Day 35+7
Title
Change in circulating ferritin
Time Frame
Any time point between injection initiation and Day 35+7
Title
Change in circulating D-dimer
Time Frame
Any time point between injection initiation and Day 35+7
Title
Change in liver function
Time Frame
Any time point between injection initiation and Day 35+7
Title
Change in other blood chemistry
Time Frame
Any time point between injection initiation and Day 35+7
Title
Change in hematology
Time Frame
Any time point between injection initiation and Day 35+7
Title
Change in inflammatory markers
Time Frame
Any time point between injection initiation and Day 35+7
Title
Change in coagulation markers
Time Frame
Any time point between injection initiation and Day 35+7
Title
Percent of clinical failure
Time Frame
Any time point between injection initiation and Day 35+7

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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). Male or female 18-85 years old hospitalized COVID-19 patients (positive local SARS-CoV2 test) 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: Patients considered unsalvageable or expected to expire within 24 hours On mechanical ventilation or imminent need for mechanical ventilation expected in the next 24 hours Evidence of acute end-organ injury in 2 or more organ systems (not including cardiac or pulmonary), such as, renal, hepatic, or CNS injury Receiving another investigational therapy for treatment or prevention of COVID-19-related hypoxemic respiratory failure or ARDS other than antiviral therapy Systolic blood pressure (SBP) < 95 mmHg and/or diastolic blood pressure (DBP) < 50 mmHg or overt symptomatic hypotension during screening Resting heart rate > 110 BPM (beats per minute) during screening 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. 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 Any in-patient surgical procedure or hospitalization (defined as > 23 hours) within 30 days of subject screening except for prior hospitalization for COVID-19 Known hypersensitivity to study drug or any of the excipients of the drug formulation Pregnant or lactating female subjects 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
Facility Information:
Facility Name
Baptist Health Research Institute
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32207
Country
United States
Facility Name
Sarasota Memorial Hospital
City
Sarasota
State/Province
Florida
ZIP/Postal Code
34239
Country
United States
Facility Name
The University of Kansas Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
Adventist Healthcare White Oak Medical Center
City
Silver Spring
State/Province
Maryland
ZIP/Postal Code
20904
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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).

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