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).

NCT04433546 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: PB1046-PT-CL-0007
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 4

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Time to clinical recovery from initiation of pemziviptadil (PB1046)

  28 days

Secondary Outcomes (15)

• Time to clinical recovery (being well enough for hospital discharge or returning to normal baseline activity level prior to discharge)

  28 days

• Time to hospital discharge

  Any time point between injection initiation and Day 28

• All-cause mortality

  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

  28 days

• 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

Other Outcomes (13)

• 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

• 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

• Incidence of multi-system organ failure (MSOF)

  Any time point between injection initiation and Day 35+7

Study Arms (3)

High Dose (100 mg) Group

EXPERIMENTAL

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

Drug: Pemziviptadil (PB1046)

Middle Dose (40 mg) Group

EXPERIMENTAL

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

Drug: Pemziviptadil (PB1046)

Low Dose (10 mg) Control Group

PLACEBO COMPARATOR

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

Drug: Low Dose (10 mg) Control

Interventions

Pemziviptadil (PB1046) DRUG

Pemziviptadil (PB1046), Once Weekly Subcutaneous Injection

High Dose (100 mg) Group; Middle Dose (40 mg) Group

Low Dose (10 mg) Control DRUG

Pemziviptadil (PB1046), Once Weekly Subcutaneous Injection (10 mg diluted in sodium chloride to match active drug volume)

Low Dose (10 mg) Control Group

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• PhaseBio Pharmaceuticals Inc.: lead

Study Sites (4)

Baptist Health Research Institute

Jacksonville, Florida, 32207, United States

Location

Sarasota Memorial Hospital

Sarasota, Florida, 34239, United States

Location

The University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Adventist Healthcare White Oak Medical Center

Silver Spring, Maryland, 20904, United States

Location

MeSH Terms

Conditions

Respiratory Distress Syndrome; Coronavirus Infections; Respiratory Insufficiency; Pneumonia; Pulmonary Edema; Cytokine Release Syndrome; COVID-19; Cardiovascular Diseases; Heart Failure; Myocardial Infarction; Dyspnea

Interventions

VIP-ELP fusion molecule PB1046

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; Pneumonia, Viral; Heart Diseases; Myocardial Ischemia; Vascular Diseases; Infarction; Ischemia; Necrosis; Signs and Symptoms, Respiratory; Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2020
• First Posted: June 16, 2020
• Study Start: July 15, 2020
• Primary Completion: December 2, 2020
• Study Completion: December 2, 2020
• Last Updated: December 11, 2020

Record last verified: 2020-12

Locations

US (4)