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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)

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ClinicalTrials.gov Identifier: NCT04433546
Recruitment Status : Terminated (Company no longer pursing indication)
First Posted : June 16, 2020
Last Update Posted : December 11, 2020
Sponsor:
Information provided by (Responsible Party):
PhaseBio Pharmaceuticals Inc.

Tracking Information
First Submitted Date  ICMJE May 28, 2020
First Posted Date  ICMJE June 16, 2020
Last Update Posted Date December 11, 2020
Actual Study Start Date  ICMJE July 15, 2020
Actual Primary Completion Date December 2, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 11, 2020)
Time to clinical recovery from initiation of pemziviptadil (PB1046) [ Time Frame: 28 days ]
Original Primary Outcome Measures  ICMJE
 (submitted: June 13, 2020)
Days alive and free of respiratory failure from initiation of PB1046 [ Time Frame: 28 days ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 11, 2020)
  • 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 [ Time Frame: 28 days ]
    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. [ Time Frame: Any time point between injection initiation and Day 28 ]
  • Change from baseline in cardiac marker troponin I (TrI) [ Time Frame: Any time point between injection initiation and Day 35+7 ]
  • Change from baseline in cardiac marker NT-proBNP/BNP [ Time Frame: Any time point between injection initiation and Day 35+7 ]
  • Change from baseline in TNF alpha [ Time Frame: Any time point between injection initiation and Day 35+7 ]
  • Change from baseline in IL-1 [ Time Frame: Any time point between injection initiation and Day 35+7 ]
  • Change from baseline in IL-6 [ Time Frame: Any time point between injection initiation and Day 35+7 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: June 13, 2020)
  • Time to clinical recovery (being well enough for hospital discharge or returning to normal baseline activity level prior to discharge) [ Time Frame: 28 days ]
  • Development of ARDS (PaO2:FiO2 ratio < 300 mm Hg) during hospitalization [ Time Frame: Any time point between injection initiation and Day 28 ]
    PaO2:FiO2 ratio is the ratio of partial pressure of arterial oxygen to percentage of inspired oxygen
  • 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 [ Time Frame: 28 days ]
    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. [ Time Frame: Any time point between injection initiation and Day 28 ]
  • Change from baseline in cardiac marker high sensitivity troponin I (hsTnI) [ Time Frame: Any time point between injection initiation and Day 35+7 ]
  • Change from baseline in cardiac marker NT-proBNP [ Time Frame: Any time point between injection initiation and Day 35+7 ]
  • Change from baseline in TNF alpha [ Time Frame: Any time point between injection initiation and Day 35+7 ]
  • Change from baseline in IL-1 [ Time Frame: Any time point between injection initiation and Day 35+7 ]
  • Change from baseline in IL-6 [ Time Frame: Any time point between injection initiation and Day 35+7 ]
  • 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 PB1046 [ Time Frame: Any time point between injection initiation and Day 35+7 ]
  • Incidence and severity of any treatment emergent adverse events (TEAEs) or serious adverse events (SAEs) as determined by vital signs and their relationship to PB1046 [ Time Frame: Any time point between injection initiation and Day 35+7 ]
  • Incidence and severity of any treatment emergent adverse events (TEAEs) or serious adverse events (SAEs) as determined by laboratory results and their relationship to PB1046 [ Time Frame: Any time point between injection initiation and Day 35+7 ]
  • 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 PB1046 [ Time Frame: Any time point between injection initiation and Day 35+7 ]
  • 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 PB1046 [ Time Frame: Any time point between injection initiation and Day 35+7 ]
Current Other Pre-specified Outcome Measures
 (submitted: November 11, 2020)
  • 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 ]
  • 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 ]
  • Incidence of multi-system organ failure (MSOF) [ Time Frame: Any time point between injection initiation and Day 35+7 ]
  • Number of multi-system organ failure (MSOF) free days [ Time Frame: Any time point between injection initiation and Day 35+7 ]
  • Number of subjects requiring extracorporeal membrane oxygenation (ECMO) [ Time Frame: Any time point between injection initiation and Day 35+7 ]
  • Change in circulating ferritin [ Time Frame: Any time point between injection initiation and Day 35+7 ]
  • Change in circulating D-dimer [ Time Frame: Any time point between injection initiation and Day 35+7 ]
  • Change in liver function [ Time Frame: Any time point between injection initiation and Day 35+7 ]
  • Change in other blood chemistry [ Time Frame: Any time point between injection initiation and Day 35+7 ]
  • Change in hematology [ Time Frame: Any time point between injection initiation and Day 35+7 ]
  • Change in inflammatory markers [ Time Frame: Any time point between injection initiation and Day 35+7 ]
  • Change in coagulation markers [ Time Frame: Any time point between injection initiation and Day 35+7 ]
  • Percent of clinical failure [ Time Frame: Any time point between injection initiation and Day 35+7 ]
Original Other Pre-specified Outcome Measures
 (submitted: June 13, 2020)
  • 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 ]
  • 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 ]
  • Incidence of multi-system organ failure (MSOF) [ Time Frame: Any time point between injection initiation and Day 35+7 ]
  • Number of multi-system organ failure (MSOF) free days [ Time Frame: Any time point between injection initiation and Day 35+7 ]
  • Number of subjects requiring extracorporeal membrane oxygenation (ECMO) [ Time Frame: Any time point between injection initiation and Day 35+7 ]
 
Descriptive Information
Brief Title  ICMJE 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).
Official Title  ICMJE 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)
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE
  • Drug: Pemziviptadil (PB1046)
    Pemziviptadil (PB1046), Once Weekly Subcutaneous Injection
  • Drug: Low Dose (10 mg) Control
    Pemziviptadil (PB1046), Once Weekly Subcutaneous Injection (10 mg diluted in sodium chloride to match active drug volume)
Study Arms  ICMJE
  • Experimental: High Dose (100 mg) Group
    High: Pemziviptadil (PB1046) 100 mg subcutaneous (SC) weekly for 4 weeks or until hospital discharge
    Intervention: Drug: Pemziviptadil (PB1046)
  • Experimental: Middle Dose (40 mg) Group
    Middle: Pemziviptadil (PB1046) 40 mg SC weekly for 4 weeks or until hospital discharge
    Intervention: Drug: Pemziviptadil (PB1046)
  • Placebo Comparator: Low Dose (10 mg) Control Group
    Low Control: Pemziviptadil (PB1046) 10 mg SC weekly for 4 weeks or until hospital discharge
    Intervention: Drug: Low Dose (10 mg) Control
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: November 11, 2020)
54
Original Estimated Enrollment  ICMJE
 (submitted: June 13, 2020)
210
Actual Study Completion Date  ICMJE December 2, 2020
Actual Primary Completion Date December 2, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04433546
Other Study ID Numbers  ICMJE PB1046-PT-CL-0007
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party PhaseBio Pharmaceuticals Inc.
Study Sponsor  ICMJE PhaseBio Pharmaceuticals Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account PhaseBio Pharmaceuticals Inc.
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP