Back to results

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

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:

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

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

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

NCT ID

NCT04433546

First Posted

May 28, 2020

Last Updated

December 9, 2020

Sponsor

PhaseBio Pharmaceuticals Inc.

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

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

Description

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