Crizanlizumab for Treating COVID-19 Vasculopathy

Phase 2

Completed

Conditions: COVID-19

Interventions: Drug: Crizanlizumab
Other: 0.9% saline

Registration Number: NCT04435184

Lead Sponsor: Johns Hopkins University

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

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

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 54

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Crizanlizumab	Crizanlizumab	Crizanlizumab is a monoclonal antibody targeting P-selectin. Crizanlizumab 5.0 mg/kg in 100 ml IV once.
Placebo Saline	0.9% saline	0.9% saline 100 ml IV once.

Primary Outcome Measures

Name	Time	Method
Soluble P-selectin Level	Day 3 after randomization or day of hospital discharge, whichever is earlier	Level of soluble P-selectin in ng/mL.

Secondary Outcome Measures

Name	Time	Method
D-dimer Level	Day 14 after randomization	Level of D-dimer in mg/L.
Time to Hospital Discharge	Up to 30 days after randomization	Time (days) to hospital discharge
Safety of Crizanlizumab as Assessed by Adverse Events	Up to day 14 after randomization	Safety of crizanlizumab will by assessed by adverse events, serious adverse events, and suspected unexpected serious adverse reactions.
Soluble P-selectin Level	Day 14 after randomization	Level of soluble P-selectin in ng/mL.
VWF Level	Day 14 after randomization	Level of VWF antigen in IU/mL.
CRP Level	Day 14 after randomization	Level of C-reactive protein (CRP) in mg/dL.
Change in Clinical Status as Assessed by the World Health Organization (WHO) Ordinal Scale for Coronavirus Disease 2019 (COVID-19) Trials	Days 3, 7 and 14 after randomization	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 1. = Ambulatory; asymptomatic; viral RNA detected 2. = Ambulatory; symptomatic; independent 3. = Ambulatory; symptomatic; assistance needed 4. = Hospitalized; no oxygen therapy 5. = Hospitalized; oxygen by mask or nasal prongs 6. = Hospitalized; oxygen by non-invasive ventilation (NIV) or high flow 7. = Hospitalized; intubation and mechanical ventilation, partial pressure of oxygen / fraction of inspired oxygen (pO2/FIO2) ≥ 150 or oxygen saturation / FIO2 (SpO2/FIO2) ≥ 200 8. = Hospitalized; intubation and mechanical ventilation, pO2/FIO2 \< 150 or SpO2/FIO2 \< 200 or vasopressors 9. = Hospitalized; intubation and mechanical ventilation, pO2/FIO2 \< 150 or SpO2/FIO2 \< 200 and vasopressors, dialysis, or extracorporeal membrane oxygenation (ECMO) 10. = Dead