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).

Overview

This is a multicenter, randomized, double-blind, parallel group study to investigate the efficacy of PB1046 by improving the clinical outcomes and increasing days alive and free of respiratory failure 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.

Full Title of Study: “A Randomized, Double-Blind, Parallel Group Study to Assess the Efficacy and Safety of Once Weekly Subcutaneous Injections of 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

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: December 18, 2020

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.

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. PB1046 is expected to improve the clinical outcomes of hospitalized COVID-19 subjects with longer survival free from respiratory failure at 28 day.

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.

Interventions

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

Arms, Groups and Cohorts

  • Experimental: High Dose (100 mg) Group
    • High: PB1046 100 mg subcutaneous (SC) weekly for 4 weeks or until hospital discharge
  • Experimental: Middle Dose (40 mg) Group
    • Middle: PB1046 40 mg SC weekly for 4 weeks or until hospital discharge
  • Placebo Comparator: Low Dose (10 mg) Control Group
    • Low Control: PB1046 10 mg SC weekly for 4 weeks or until hospital discharge

Clinical Trial Outcome Measures

Primary Measures

  • Days alive and free of respiratory failure from initiation of PB1046
    • Time Frame: 28 days

Secondary Measures

  • 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

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 85 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • PhaseBio Pharmaceuticals Inc.
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Contact(s)
    • Clinical Trials, 888-521-2805, Clinicaltrials@phasebio.com

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