Clinical trial NCT04435184: Crizanlizumab for Treating COVID-19 Vasculopathy
Official title: Crizanlizumab for Treating COVID-19 Vasculopathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: COVID-19
Keywords: coronavirus
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: Novartis
name: Socar Research SA
name: Brigham and Women's Hospital
First posted: 2020-06-17
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double-blind, placebo-controlled, randomized interventional trial.
Primary purpose: TREATMENT

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

Eligibility 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 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

Primary outcomes:
measure: Soluble P-selectin Level
timeFrame: Day 3 after randomization or day of hospital discharge, whichever is earlier
Secondary outcomes:
measure: Soluble P-selectin Level
timeFrame: Day 7 after randomization
measure: Soluble P-selectin Level
timeFrame: Day 14 after randomization
measure: D-dimer Level
timeFrame: Day 3 after randomization
measure: D-dimer Level
timeFrame: Day 7 after randomization
measure: D-dimer Level
timeFrame: Day 14 after randomization
measure: VWF Level
timeFrame: Day 3 after randomization
measure: VWF Level
timeFrame: Day 7 after randomization
measure: VWF Level
timeFrame: Day 14 after randomization
measure: CRP Level
timeFrame: Day 3 after randomization
measure: CRP Level
timeFrame: Day 7 after randomization
measure: CRP Level
timeFrame: Day 14 after randomization
measure: Change in Clinical Status as Assessed by the World Health Organization (WHO) Ordinal Scale for Coronavirus Disease 2019 (COVID-19) Trials
timeFrame: Days 3, 7 and 14 after randomization
measure: Time to Hospital Discharge
timeFrame: Up to 30 days after randomization
measure: Safety of Crizanlizumab as Assessed by Adverse Events
timeFrame: Up to day 14 after randomization
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Charles J Lowenstein, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.