Crizanlizumab for Treating COVID-19 Vasculopathy

NCT ID: NCT04435184

Last Updated: 2021-11-09

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

54 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-07-09

Study Completion Date

2021-01-04

Brief Summary

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

Detailed Description

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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

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COVID-19

Keywords

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coronavirus

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Double-blind, placebo-controlled, randomized interventional trial.
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Crizanlizumab

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

Group Type EXPERIMENTAL

Crizanlizumab

Intervention Type DRUG

Crizanlizumab 5.0 mg/kg in 100 ml IV once.

Placebo Saline

0.9% saline 100 ml IV once.

Group Type ACTIVE_COMPARATOR

0.9% saline

Intervention Type OTHER

0.9% saline 100 ml IV once.

Interventions

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Crizanlizumab

Crizanlizumab 5.0 mg/kg in 100 ml IV once.

Intervention Type DRUG

0.9% saline

0.9% saline 100 ml IV once.

Intervention Type OTHER

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis

INDUSTRY

Sponsor Role collaborator

Socar Research SA

NETWORK

Sponsor Role collaborator

Brigham and Women's Hospital

OTHER

Sponsor Role collaborator

Johns Hopkins University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Charles J Lowenstein, MD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

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Johns Hopkins Hospital

Baltimore, Maryland, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 27959701 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34904132 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33186055 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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IRB00249874

Identifier Type: -

Identifier Source: org_study_id