Crizanlizumab for Treating COVID-19 Vasculopathy

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

Detailed Description
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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

Official Title
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Crizanlizumab for Treating COVID-19 Vasculopathy

Conditions
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COVID-19

Intervention / Treatment
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* Drug: Crizanlizumab
* Other: 0.9% saline


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double-blind, placebo-controlled, randomized interventional trial.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Crizanlizumab<br>Crizanlizumab is a monoclonal antibody targeting P-selectin. Crizanlizumab 5.0 mg/kg in 100 ml IV once. | Drug: Crizanlizumab<br>* Crizanlizumab 5.0 mg/kg in 100 ml IV once.<br>|
| Active Comparator: Placebo Saline<br>0.9% saline 100 ml IV once. | Other: 0.9% saline<br>* 0.9% saline 100 ml IV once.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Soluble P-selectin Level | Level of soluble P-selectin in ng/mL. | Day 3 after randomization or day of hospital discharge, whichever is earlier | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Soluble P-selectin Level | Level of soluble P-selectin in ng/mL. | Day 7 after randomization | 
| Soluble P-selectin Level | Level of soluble P-selectin in ng/mL. | Day 14 after randomization | 
| D-dimer Level | Level of D-dimer in mg/L. | Day 3 after randomization | 
| D-dimer Level | Level of D-dimer in mg/L. | Day 7 after randomization | 
| D-dimer Level | Level of D-dimer in mg/L. | Day 14 after randomization | 
| VWF Level | Level of von Willebrand Factor (VWF) antigen in IU/mL. | Day 3 after randomization | 
| VWF Level | Level of VWF antigen in IU/mL. | Day 7 after randomization | 
| VWF Level | Level of VWF antigen in IU/mL. | Day 14 after randomization | 
| CRP Level | Level of C-reactive protein (CRP) in mg/dL. | Day 3 after randomization | 
| CRP Level | Level of C-reactive protein (CRP) in mg/dL. | Day 7 after randomization | 
| CRP Level | Level of C-reactive protein (CRP) in mg/dL. | Day 14 after randomization | 
| Change in Clinical Status as Assessed by the World Health Organization (WHO) Ordinal Scale for Coronavirus Disease 2019 (COVID-19) Trials | Change in the clinical status over 14 days as measured by an ordinal scale that is the first assessment of the clinical status on a given study day. The scale is as follows: 0 = Uninfected; no viral RNA detected = Ambulatory; asymptomatic; viral RNA detected = Ambulatory; symptomatic; independent = Ambulatory; symptomatic; assistance needed = Hospitalized; no oxygen therapy = Hospitalized; oxygen by mask or nasal prongs = Hospitalized; oxygen by non-invasive ventilation (NIV) or high flow = Hospitalized; intubation and mechanical ventilation, partial pressure of oxygen / fraction of inspired oxygen (pO2/FIO2) ≥ 150 or oxygen saturation / FIO2 (SpO2/FIO2) ≥ 200 = Hospitalized; intubation and mechanical ventilation, pO2/FIO2 < 150 or SpO2/FIO2 < 200 or vasopressors = Hospitalized; intubation and mechanical ventilation, pO2/FIO2 < 150 or SpO2/FIO2 < 200 and vasopressors, dialysis, or extracorporeal membrane oxygenation (ECMO) = Dead | Days 3, 7 and 14 after randomization | 
| Time to Hospital Discharge | Time (days) to hospital discharge | Up to 30 days after randomization | 
| Safety of Crizanlizumab as Assessed by Adverse Events | Safety of crizanlizumab will by assessed by adverse events, serious adverse events, and suspected unexpected serious adverse reactions. | Up to day 14 after randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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coronavirus