Crizanlizumab for Treating COVID-19 Vasculopathy

COVID-19 Clinical Trial

— CRITICAL  

Official title:

Crizanlizumab for Treating COVID-19 Vasculopathy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04435184
• Other study ID #: IRB00249874
• Status: Completed
• Phase: Phase 2
• Start date: July 9, 2020
• Est. completion date: January 4, 2021

Study information

• Verified date: November 2021
• Source: Johns Hopkins University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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 information / eligibility

• Status: Completed
• Enrollment: 54
• Est. completion date: January 4, 2021
• Est. primary completion date: November 28, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COVID-19

Intervention

Drug:
• Crizanlizumab
Crizanlizumab 5.0 mg/kg in 100 ml IV once.

Other:
• 0.9% saline
0.9% saline 100 ml IV once.

Locations

Country	Name	City	State
United States	Johns Hopkins Hospital	Baltimore	Maryland

Sponsors (4)

Lead Sponsor	Collaborator
Johns Hopkins University	Brigham and Women's Hospital, Novartis, Socar Research SA

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Soluble P-selectin Level	Level of soluble P-selectin in ng/mL.	Day 3 after randomization or day of hospital discharge, whichever is earlier
Secondary	Soluble P-selectin Level	Level of soluble P-selectin in ng/mL.	Day 7 after randomization
Secondary	Soluble P-selectin Level	Level of soluble P-selectin in ng/mL.	Day 14 after randomization
Secondary	D-dimer Level	Level of D-dimer in mg/L.	Day 3 after randomization
Secondary	D-dimer Level	Level of D-dimer in mg/L.	Day 7 after randomization
Secondary	D-dimer Level	Level of D-dimer in mg/L.	Day 14 after randomization
Secondary	VWF Level	Level of von Willebrand Factor (VWF) antigen in IU/mL.	Day 3 after randomization
Secondary	VWF Level	Level of VWF antigen in IU/mL.	Day 7 after randomization
Secondary	VWF Level	Level of VWF antigen in IU/mL.	Day 14 after randomization
Secondary	CRP Level	Level of C-reactive protein (CRP) in mg/dL.	Day 3 after randomization
Secondary	CRP Level	Level of C-reactive protein (CRP) in mg/dL.	Day 7 after randomization
Secondary	CRP Level	Level of C-reactive protein (CRP) in mg/dL.	Day 14 after randomization
Secondary	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	Days 3, 7 and 14 after randomization
Secondary	Time to Hospital Discharge	Time (days) to hospital discharge	Up to 30 days after randomization
Secondary	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.	Up to day 14 after randomization