The purpose of this trial is to test the efficacy and safety of crizanlizumab in patients hospitalized with COVID-19.
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
Drug: Crizanlizumab
Crizanlizumab 5.0 mg/kg in 100 ml IV once.
Other: 0.9% saline
0.9% saline 100 ml IV once.
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
Johns Hopkins Hospital
Baltimore, Maryland, United States
Charles J Lowenstein, MD, Principal Investigator
Johns Hopkins University