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Crizanlizumab for Treating COVID-19 Vasculopathy (CRITICAL)

Primary Purpose

COVID-19

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Crizanlizumab
0.9% saline
Sponsored by
Johns Hopkins University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for COVID-19 focused on measuring coronavirus

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 D-Dimer > 0.49 mg/L
  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

Sites / Locations

  • Johns Hopkins Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Crizanlizumab

Placebo Saline

Arm Description

Crizanlizumab is a monoclonal antibody targeting P-selectin. Crizanlizumab 5.0 mg/kg in 100 ml IV once.

0.9% saline 100 ml IV once.

Outcomes

Primary Outcome Measures

Soluble P-selectin Level
Level of soluble P-selectin in ng/mL.

Secondary Outcome Measures

Soluble P-selectin Level
Level of soluble P-selectin in ng/mL.
Soluble P-selectin Level
Level of soluble P-selectin in ng/mL.
D-dimer Level
Level of D-dimer in mg/L.
D-dimer Level
Level of D-dimer in mg/L.
D-dimer Level
Level of D-dimer in mg/L.
VWF Level
Level of von Willebrand Factor (VWF) antigen in IU/mL.
VWF Level
Level of VWF antigen in IU/mL.
VWF Level
Level of VWF antigen in IU/mL.
CRP Level
Level of C-reactive protein (CRP) in mg/dL.
CRP Level
Level of C-reactive protein (CRP) in mg/dL.
CRP Level
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
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 (days) to hospital discharge
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.

Full Information

First Posted
June 16, 2020
Last Updated
November 3, 2021
Sponsor
Johns Hopkins University
Collaborators
Novartis, Socar Research SA, Brigham and Women's Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT04435184
Brief Title
Crizanlizumab for Treating COVID-19 Vasculopathy
Acronym
CRITICAL
Official Title
Crizanlizumab for Treating COVID-19 Vasculopathy
Study Type
Interventional

2. Study Status

Record Verification Date
November 2021
Overall Recruitment Status
Completed
Study Start Date
July 9, 2020 (Actual)
Primary Completion Date
November 28, 2020 (Actual)
Study Completion Date
January 4, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Johns Hopkins University
Collaborators
Novartis, Socar Research SA, Brigham and Women's Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19
Keywords
coronavirus

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Double-blind, placebo-controlled, randomized interventional trial.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
54 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Crizanlizumab
Arm Type
Experimental
Arm Description
Crizanlizumab is a monoclonal antibody targeting P-selectin. Crizanlizumab 5.0 mg/kg in 100 ml IV once.
Arm Title
Placebo Saline
Arm Type
Active Comparator
Arm Description
0.9% saline 100 ml IV once.
Intervention Type
Drug
Intervention Name(s)
Crizanlizumab
Intervention Description
Crizanlizumab 5.0 mg/kg in 100 ml IV once.
Intervention Type
Other
Intervention Name(s)
0.9% saline
Intervention Description
0.9% saline 100 ml IV once.
Primary Outcome Measure Information:
Title
Soluble P-selectin Level
Description
Level of soluble P-selectin in ng/mL.
Time Frame
Day 3 after randomization or day of hospital discharge, whichever is earlier
Secondary Outcome Measure Information:
Title
Soluble P-selectin Level
Description
Level of soluble P-selectin in ng/mL.
Time Frame
Day 7 after randomization
Title
Soluble P-selectin Level
Description
Level of soluble P-selectin in ng/mL.
Time Frame
Day 14 after randomization
Title
D-dimer Level
Description
Level of D-dimer in mg/L.
Time Frame
Day 3 after randomization
Title
D-dimer Level
Description
Level of D-dimer in mg/L.
Time Frame
Day 7 after randomization
Title
D-dimer Level
Description
Level of D-dimer in mg/L.
Time Frame
Day 14 after randomization
Title
VWF Level
Description
Level of von Willebrand Factor (VWF) antigen in IU/mL.
Time Frame
Day 3 after randomization
Title
VWF Level
Description
Level of VWF antigen in IU/mL.
Time Frame
Day 7 after randomization
Title
VWF Level
Description
Level of VWF antigen in IU/mL.
Time Frame
Day 14 after randomization
Title
CRP Level
Description
Level of C-reactive protein (CRP) in mg/dL.
Time Frame
Day 3 after randomization
Title
CRP Level
Description
Level of C-reactive protein (CRP) in mg/dL.
Time Frame
Day 7 after randomization
Title
CRP Level
Description
Level of C-reactive protein (CRP) in mg/dL.
Time Frame
Day 14 after randomization
Title
Change in Clinical Status as Assessed by the World Health Organization (WHO) Ordinal Scale for Coronavirus Disease 2019 (COVID-19) Trials
Description
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 Frame
Days 3, 7 and 14 after randomization
Title
Time to Hospital Discharge
Description
Time (days) to hospital discharge
Time Frame
Up to 30 days after randomization
Title
Safety of Crizanlizumab as Assessed by Adverse Events
Description
Safety of crizanlizumab will by assessed by adverse events, serious adverse events, and suspected unexpected serious adverse reactions.
Time Frame
Up to day 14 after randomization

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Charles J Lowenstein, MD
Organizational Affiliation
Johns Hopkins University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Johns Hopkins Hospital
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
27959701
Citation
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.
Results Reference
background
PubMed Identifier
34904132
Citation
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.
Results Reference
derived
PubMed Identifier
33186055
Citation
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.
Results Reference
derived

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Crizanlizumab for Treating COVID-19 Vasculopathy

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