Crizanlizumab for Treating COVID-19 Vasculopathy

Overview

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

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: October 1, 2020

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

Interventions

  • Drug: Crizanlizumab
    • Crizanlizumab 5.0 mg/kg in 100 ml IV once.
  • Other: 0.9% saline
    • 0.9% saline 100 ml IV once.

Arms, Groups and Cohorts

  • Experimental: Crizanlizumab
    • Crizanlizumab is a monoclonal antibody targeting P-selectin. Crizanlizumab 5.0 mg/kg in 100 ml IV once.
  • Active Comparator: Placebo Saline
    • 0.9% saline 100 ml IV once.

Clinical Trial Outcome Measures

Primary Measures

  • Soluble P-selectin level
    • Time Frame: Day 7 after randomization
    • Level of soluble P-selectin in ng/ml.

Secondary Measures

  • Soluble P-selectin level
    • Time Frame: Day 14 after randomization
    • Level of soluble P-selectin in ng/ml.
  • D-dimer level
    • Time Frame: Day 7 after randomization
    • Level of D-dimer in mg/L.
  • D-dimer level
    • Time Frame: Day 14 after randomization
    • Level of D-dimer in mg/L.
  • VWF level
    • Time Frame: Day 7 after randomization
    • Level of VWF antigen (percentage).
  • VWF level
    • Time Frame: Day 14 after randomization
    • Level of VWF antigen in (percentage).
  • CRP level
    • Time Frame: Day 7 after randomization
    • Level of C-reactive protein (CRP) in mg/dL.
  • CRP level
    • Time Frame: 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 COVID-19 Trials
    • Time Frame: Daily up to day 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 = 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
  • Time to hospital discharge
    • Time Frame: Up to 30 days after randomization
    • Time (days) to hospital discharge
  • Safety of Crizanlizumab as assessed by adverse events
    • Time Frame: Up to day 14 after randomization
    • Safety of crizanlizumab will by assessed by adverse events, serious adverse events, and suspected unexpected serious adverse reactions.

Participating in This Clinical Trial

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 VWF antigen levels > 150%

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Johns Hopkins University
  • Collaborator
    • Novartis
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Charles J Lowenstein, MD, Principal Investigator, Johns Hopkins University
  • Overall Contact(s)
    • Charles Lowenstein, MD, (410) 955-3097, clowens1@jhmi.edu

References

Ataga KI, Kutlar A, Kanter J, Liles D, Cancado R, Friedrisch J, Guthrie TH, Knight-Madden J, Alvarez OA, Gordeuk VR, Gualandro S, Colella MP, Smith WR, Rollins SA, Stocker JW, Rother RP. Crizanlizumab for the Prevention of Pain Crises in Sickle Cell Disease. N Engl J Med. 2017 Feb 2;376(5):429-439. doi: 10.1056/NEJMoa1611770. Epub 2016 Dec 3.

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.