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Crizanlizumab for Treating COVID-19 Vasculopathy (CRITICAL)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04435184
Recruitment Status : Not yet recruiting
First Posted : June 17, 2020
Last Update Posted : June 17, 2020
Sponsor:
Collaborators:
Novartis
Socar Research SA
Brigham and Women's Hospital
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
COVID-19 Drug: Crizanlizumab Other: 0.9% saline Phase 2

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Double-blind, placebo-controlled, randomized interventional trial.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Crizanlizumab for Treating COVID-19 Vasculopathy
Estimated Study Start Date : June 2020
Estimated Primary Completion Date : October 2020
Estimated Study Completion Date : October 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Crizanlizumab
Crizanlizumab is a monoclonal antibody targeting P-selectin. Crizanlizumab 5.0 mg/kg in 100 ml IV once.
Drug: Crizanlizumab
Crizanlizumab 5.0 mg/kg in 100 ml IV once.

Active Comparator: Placebo Saline
0.9% saline 100 ml IV once.
Other: 0.9% saline
0.9% saline 100 ml IV once.




Primary Outcome Measures :
  1. Soluble P-selectin level [ Time Frame: Day 7 after randomization ]
    Level of soluble P-selectin in ng/ml.


Secondary Outcome Measures :
  1. Soluble P-selectin level [ Time Frame: Day 14 after randomization ]
    Level of soluble P-selectin in ng/ml.

  2. D-dimer level [ Time Frame: Day 7 after randomization ]
    Level of D-dimer in mg/L.

  3. D-dimer level [ Time Frame: Day 14 after randomization ]
    Level of D-dimer in mg/L.

  4. VWF level [ Time Frame: Day 7 after randomization ]
    Level of VWF antigen (percentage).

  5. VWF level [ Time Frame: Day 14 after randomization ]
    Level of VWF antigen in (percentage).

  6. CRP level [ Time Frame: Day 7 after randomization ]
    Level of C-reactive protein (CRP) in mg/dL.

  7. CRP level [ Time Frame: Day 14 after randomization ]
    Level of C-reactive protein (CRP) in mg/dL.

  8. 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

    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

  9. Time to hospital discharge [ Time Frame: Up to 30 days after randomization ]
    Time (days) to hospital discharge

  10. 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04435184


Contacts
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Contact: Charles Lowenstein, MD (410) 955-3097 clowens1@jhmi.edu
Contact: Thorsten Leucker, MD PhD ‭(410) 502-9453‬ tleucke1@jhmi.edu

Locations
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United States, Maryland
Johns Hopkins Hospital
Baltimore, Maryland, United States, 21287
Contact: Charles J Lowenstein, MD    410-955-3097    clowens1@jhmi.edu   
Contact: Shannon Kelley, BS    ‭(410) 688-9934‬    skelle31@jhu.edu   
Sponsors and Collaborators
Johns Hopkins University
Novartis
Socar Research SA
Brigham and Women's Hospital
Investigators
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Principal Investigator: Charles J Lowenstein, MD Johns Hopkins University
Publications:
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Responsible Party: Johns Hopkins University
ClinicalTrials.gov Identifier: NCT04435184    
Other Study ID Numbers: IRB00249874
First Posted: June 17, 2020    Key Record Dates
Last Update Posted: June 17, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Johns Hopkins University:
coronavirus
Additional relevant MeSH terms:
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Vascular Diseases
Cardiovascular Diseases