Crizanlizumab for Treating COVID-19 Vasculopathy

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

Inclusion criteria

• Willing to provide written informed consent
• Willing to comply with all study procedures and be available for the duration of the study
• Male or female ≥ 18 years of age
• 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))
• Currently hospitalized
• Symptoms of acute respiratory infection (at least one of the following: cough, fever > 37.5°C, dyspnea, sore throat, anosmia),
• Radiographic evidence of pulmonary infiltrates
• Requiring supplemental oxygen or the peripheral capillary oxygenation saturation (SpO2) < 94% on room air at screening
• Elevated D-Dimer > 0.49 mg/L
• Negative pregnancy test for females of childbearing potential

Exclusion criteria

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