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COVID-19Phase 2CRITICALNCT04435184

Crizanlizumab for Treating COVID-19 Vasculopathy

A Phase 2 study testing Crizanlizumab and 0.9% saline in people with COVID-19, run by Johns Hopkins University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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

Who is it for?
Ages 18 years and older
Conditions the study is for
COVID-19
What is being tested?
Crizanlizumab and 0.9% saline
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
54 participants
Where
1 siteUnited States
Study dates
9 Jul 2020to 4 Jan 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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),
Show all 10Show fewer
  • 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

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Johns Hopkins Hospital

    Baltimore, Maryland, 21287

Other trials in United States

About this study

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

Read the 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

Conditions
COVID-19
Being tested
Crizanlizumab, 0.9% saline
Keywords
coronavirus
Medical subject headings
COVID-19, Coronavirus Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CrizanlizumabDrug

    Crizanlizumab 5.0 mg/kg in 100 ml IV once.

  • 0.9% salineOther

    0.9% saline 100 ml IV once.

Study groups in NCT04435184
Study groupRoleWhat they receive
CrizanlizumabExperimentalCrizanlizumab is a monoclonal antibody targeting P-selectin. Crizanlizumab 5.0 mg/kg in 100 ml IV once.
Receives: Drug: Crizanlizumab
Placebo SalineActive comparator0.9% saline 100 ml IV once.
Receives: Other: 0.9% saline

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Soluble P-selectin Level

    Level of soluble P-selectin in ng/mL.

    Measured: Day 3 after randomization or day of hospital discharge, whichever is earlier

Secondary outcomes (14)

  1. Soluble P-selectin Level

    Level of soluble P-selectin in ng/mL.

    Measured: Day 7 after randomization

  2. Soluble P-selectin Level

    Level of soluble P-selectin in ng/mL.

    Measured: Day 14 after randomization

  3. D-dimer Level

    Level of D-dimer in mg/L.

    Measured: Day 3 after randomization

  4. D-dimer Level

    Level of D-dimer in mg/L.

    Measured: Day 7 after randomization

  5. D-dimer Level

    Level of D-dimer in mg/L.

    Measured: Day 14 after randomization

  6. VWF Level

    Level of von Willebrand Factor (VWF) antigen in IU/mL.

    Measured: Day 3 after randomization

  7. VWF Level

    Level of VWF antigen in IU/mL.

    Measured: Day 7 after randomization

  8. VWF Level

    Level of VWF antigen in IU/mL.

    Measured: Day 14 after randomization

  9. CRP Level

    Level of C-reactive protein (CRP) in mg/dL.

    Measured: Day 3 after randomization

  10. CRP Level

    Level of C-reactive protein (CRP) in mg/dL.

    Measured: Day 7 after randomization

  11. CRP Level

    Level of C-reactive protein (CRP) in mg/dL.

    Measured: Day 14 after randomization

  12. 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

    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

    Measured: Days 3, 7 and 14 after randomization

  13. Time to Hospital Discharge

    Time (days) to hospital discharge

    Measured: Up to 30 days after randomization

  14. 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.

    Measured: Up to day 14 after randomization

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Jun 2020
  2. Study start9 Jul 2020
  3. Primary completion28 Nov 2020
  4. Study completion4 Jan 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Double-blind, placebo-controlled, randomized interventional trial.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
54 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04435184
Sponsor's protocol ID
IRB00249874
Acronym
CRITICAL
Status last verified
Nov 2021
First submitted
16 Jun 2020
Last updated
9 Nov 2021
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 27959701

  • Leucker TM, Osburn WO, Reventun P, Smith K, Claggett B, Kirwan BA, de Brouwer S, Williams MS, Gerstenblith G, Hager DN, Streiff MB, Solomon SD, Lowenstein CJ. Effect of Crizanlizumab, a P-Selectin Inhibitor, in COVID-19: A Placebo-Controlled, Randomized Trial. JACC Basic Transl Sci. 2021 Dec;6(12):935-945. doi: 10.1016/j.jacbts.2021.09.013. Epub 2021 Dec 8.

    PubMed 34904132

  • Metkus TS, Sokoll LJ, Barth AS, Czarny MJ, Hays AG, Lowenstein CJ, Michos ED, Nolley EP, Post WS, Resar JR, Thiemann DR, Trost JC, Hasan RK. Myocardial Injury in Severe COVID-19 Compared With Non-COVID-19 Acute Respiratory Distress Syndrome. Circulation. 2021 Feb 9;143(6):553-565. doi: 10.1161/CIRCULATIONAHA.120.050543. Epub 2020 Nov 13.

    PubMed 33186055

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Crizanlizumab and 0.9% saline in people with COVID-19, run by Johns Hopkins University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Nov 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Soluble P-selectin Level (time frame: Day 3 after randomization or day of hospital discharge, whichever is earlier). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04435184, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Nov 2021.

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