Crizanlizumab for Treating COVID-19 Vasculopathy (CRITICAL)

Johns Hopkins University

Status and phase: Completed; Phase 2

Conditions: COVID-19

Treatments: Other: 0.9% saline; Drug: Crizanlizumab

Study type: Interventional

Funder types: Other; NETWORK; Industry

Identifiers

NCT04435184

IRB00249874

Details and patient eligibility

About

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

Full 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

Enrollment: 54 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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54 participants in 2 patient groups

Crizanlizumab

Experimental group

Description:

Crizanlizumab is a monoclonal antibody targeting P-selectin. Crizanlizumab 5.0 mg/kg in 100 ml IV once.

Treatment:

Drug: Crizanlizumab

Placebo Saline

Active Comparator group

Description:

0.9% saline 100 ml IV once.

Treatment:

Other: 0.9% saline