Crizanlizumab for Treating COVID-19 Vasculopathy

Purpose

The purpose of this trial is to test the efficacy and safety of crizanlizumab in patients hospitalized with COVID-19.

Condition

  • COVID-19

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  1. Willing to provide written informed consent 2. Willing to comply with all study procedures and be available for the duration of the study 3. Male or female ≥ 18 years of age 4. SARS-CoV-2 infection (COVID-19) within the past 10 d documented by laboratory test (nucleic acid test (NAT) or reverse transcriptase-polymerase chain reaction (RT-PCR)) 5. Currently hospitalized 6. Symptoms of acute respiratory infection (at least one of the following: cough, fever > 37.5°C, dyspnea, sore throat, anosmia), 7. Radiographic evidence of pulmonary infiltrates 8. Requiring supplemental oxygen or the peripheral capillary oxygenation saturation (SpO2) < 94% on room air at screening 9. Elevated D-Dimer > 0.49 mg/L 10. Negative pregnancy test for females of childbearing potential

Exclusion Criteria

  1. Use of home oxygen at baseline 2. Current use of mechanical ventilation 3. Inability to provide consent 4. Do not intubate status 5. Prisoner or incarcerated 6. Pregnancy or Breast Feeding 7. Participation in other interventional therapy trials for COVID-19. 8. International normalized ratio (INR) > 3 or activated partial thromboplastin time (aPTT) > 60

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Double-blind, placebo-controlled, randomized interventional trial.
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Crizanlizumab 		Crizanlizumab is a monoclonal antibody targeting P-selectin. Crizanlizumab 5.0 mg/kg in 100 ml IV once.
  • Drug: Crizanlizumab
    Crizanlizumab 5.0 mg/kg in 100 ml IV once.
Active Comparator
Placebo Saline 		0.9% saline 100 ml IV once.
  • Other: 0.9% saline
    0.9% saline 100 ml IV once.

Recruiting Locations

More Details

NCT ID
NCT04435184
Status
Completed
Sponsor
Johns Hopkins University

Detailed Description

Infection with severe acute respiratory syndrome (SARS) coronavirus 2 (CoV-2) causes coronavirus disease 2019 (COVID-19). The clinical course of COVID-19 is variable, and some patients develop severe pneumonia, multi-organ failure, and shock. Severe COVID-19 is characterized by a hyper-inflammatory and hyper-thrombotic state. We propose that this state is caused by viral injury of the vascular endothelium, leading to endothelial release of von Willebrand Factor (VWF) and P-selectin, which in turn drive thrombosis and vascular inflammation. Crizanlizumab is a monoclonal antibody that targets P-selectin. Crizanlizumab can decrease inflammation by binding to P-selectin, blocking leucocyte and platelet adherence to the vessel wall. We now plan to test the safety and efficacy of crizanlizumab in decreasing biomarkers of inflammation and thrombosis in a placebo-controlled, double-blind randomized clinical trial