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| Name | Class |
|---|---|
| Novartis | INDUSTRY |
| Socar Research SA | NETWORK |
| Brigham and Women's Hospital | OTHER |
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The purpose of this trial is to test the efficacy and safety of crizanlizumab in patients hospitalized with COVID-19.
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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Crizanlizumab | Experimental | Crizanlizumab is a monoclonal antibody targeting P-selectin. Crizanlizumab 5.0 mg/kg in 100 ml IV once. |
|
| Placebo Saline | Active Comparator | 0.9% saline 100 ml IV once. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Crizanlizumab | Drug | Crizanlizumab 5.0 mg/kg in 100 ml IV once. |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Soluble P-selectin Level | Level of soluble P-selectin in ng/mL. | Day 3 after randomization or day of hospital discharge, whichever is earlier |
| Measure | Description | Time Frame |
|---|---|---|
| Soluble P-selectin Level | Level of soluble P-selectin in ng/mL. | Day 7 after randomization |
| Soluble P-selectin Level | Level of soluble P-selectin in ng/mL. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Charles J Lowenstein, MD | Johns Hopkins University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Johns Hopkins Hospital | Baltimore | Maryland | 21287 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27959701 | Background | 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. | |
| 34904132 |
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Out of the 27 assigned to receive crizanlizumab, 2 did not receive crizanlizumab because of early discharge or early intubation. Out of the 27 assigned to receive placebo, 2 did not receive placebo because of early discharge or withdrawn consent.
From July 15, 2020 through November 27, 2020, 583 patients were screened at 3 hospitals within the Johns Hopkins Health System. A total of 54 patients who fulfilled study entry criteria were randomized to receive crizanlizumab (n = 27) or placebo (n = 27).
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| ID | Title | Description |
|---|---|---|
| FG000 | Crizanlizumab | Crizanlizumab is a monoclonal antibody targeting P-selectin. Crizanlizumab 5.0 mg/kg in 100 ml IV once. Crizanlizumab: Crizanlizumab 5.0 mg/kg in 100 ml IV once. |
| FG001 | Placebo Saline | 0.9% saline 100 ml IV once. 0.9% saline: 0.9% saline 100 ml IV once. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Baseline characteristics data was collected for the 42 participants who completed the study.
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| ID | Title | Description |
|---|---|---|
| BG000 | Crizanlizumab | Crizanlizumab is a monoclonal antibody targeting P-selectin. Crizanlizumab 5.0 mg/kg in 100 ml IV once. Crizanlizumab: Crizanlizumab 5.0 mg/kg in 100 ml IV once. |
| BG001 | Placebo Saline |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Soluble P-selectin Level | Level of soluble P-selectin in ng/mL. | Posted | Mean | Standard Deviation | ng/mL | Day 3 after randomization or day of hospital discharge, whichever is earlier |
|
30 days
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Crizanlizumab | Crizanlizumab is a monoclonal antibody targeting P-selectin. Crizanlizumab 5.0 mg/kg in 100 ml IV once. Crizanlizumab: Crizanlizumab 5.0 mg/kg in 100 ml IV once. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| multi-organ failure | General disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Charles Lowenstein | Johns Hopkins University - Baltimore, MD | 4105020391 | clowens1@jhmi.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Dec 14, 2020 | Oct 22, 2021 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| D018352 | Coronavirus Infections |
| ID | Term |
|---|---|
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
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| ID | Term |
|---|---|
| C000614139 | crizanlizumab |
| D000077330 | Saline Solution |
| ID | Term |
|---|---|
| D000077324 | Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |
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Double-blind, placebo-controlled, randomized interventional trial.
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| 0.9% saline |
| Other |
0.9% saline 100 ml IV once. |
|
| Day 14 after randomization |
| D-dimer Level | Level of D-dimer in mg/L. | Day 3 after randomization |
| D-dimer Level | Level of D-dimer in mg/L. | Day 7 after randomization |
| D-dimer Level | Level of D-dimer in mg/L. | Day 14 after randomization |
| VWF Level | Level of von Willebrand Factor (VWF) antigen in IU/mL. | Day 3 after randomization |
| VWF Level | Level of VWF antigen in IU/mL. | Day 7 after randomization |
| VWF Level | Level of VWF antigen in IU/mL. | Day 14 after randomization |
| CRP Level | Level of C-reactive protein (CRP) in mg/dL. | Day 3 after randomization |
| CRP Level | Level of C-reactive protein (CRP) in mg/dL. | Day 7 after randomization |
| CRP Level | Level of C-reactive protein (CRP) in mg/dL. | Day 14 after randomization |
| 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
| Days 3, 7 and 14 after randomization |
| Time to Hospital Discharge | Time (days) to hospital discharge | Up to 30 days after randomization |
| 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 |
| 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. |
| 33186055 | Derived | 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. |
0.9% saline 100 ml IV once.
0.9% saline: 0.9% saline 100 ml IV once.
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Units |
|---|
| Counts |
|---|
| Participants |
|
|
| Secondary | Soluble P-selectin Level | Level of soluble P-selectin in ng/mL. | Posted | Mean | Standard Deviation | ng/mL | Day 7 after randomization |
|
|
|
| Secondary | Soluble P-selectin Level | Level of soluble P-selectin in ng/mL. | Posted | Mean | Standard Deviation | ng/mL | Day 14 after randomization |
|
|
|
| Secondary | D-dimer Level | Level of D-dimer in mg/L. | Posted | Median | Inter-Quartile Range | mg/L | Day 3 after randomization |
|
|
|
| Secondary | D-dimer Level | Level of D-dimer in mg/L. | Posted | Median | Inter-Quartile Range | mg/L | Day 7 after randomization |
|
|
|
| Secondary | D-dimer Level | Level of D-dimer in mg/L. | Posted | Median | Inter-Quartile Range | mg/L | Day 14 after randomization |
|
|
|
| Secondary | VWF Level | Level of von Willebrand Factor (VWF) antigen in IU/mL. | Posted | Median | Inter-Quartile Range | IU/mL | Day 3 after randomization |
|
|
|
| Secondary | VWF Level | Level of VWF antigen in IU/mL. | Posted | Median | Inter-Quartile Range | IU/mL | Day 7 after randomization |
|
|
|
| Secondary | VWF Level | Level of VWF antigen in IU/mL. | Posted | Median | Inter-Quartile Range | IU/mL | Day 14 after randomization |
|
|
|
| Secondary | CRP Level | Level of C-reactive protein (CRP) in mg/dL. | Posted | Median | Inter-Quartile Range | mg/dL | Day 3 after randomization |
|
|
|
| Secondary | CRP Level | Level of C-reactive protein (CRP) in mg/dL. | Posted | Median | Inter-Quartile Range | mg/dL | Day 7 after randomization |
|
|
|
| Secondary | CRP Level | Level of C-reactive protein (CRP) in mg/dL. | Posted | Median | Inter-Quartile Range | 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
| Posted | Count of Participants | Participants | Days 3, 7 and 14 after randomization |
|
|
|
| Secondary | Time to Hospital Discharge | Time (days) to hospital discharge | Posted | Mean | Standard Deviation | days | 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. | Posted | Number | total adverse events | Up to day 14 after randomization |
|
|
|
| 0 |
| 25 |
| 0 |
| 25 |
| 7 |
| 25 |
| EG001 | Placebo Saline | 0.9% saline 100 ml IV once. 0.9% saline: 0.9% saline 100 ml IV once. | 0 | 25 | 1 | 25 | 5 | 25 |
| Venous thrombembolism | Vascular disorders | Systematic Assessment |
|
| Altered mental status | Nervous system disorders | Systematic Assessment |
|
| Chest pain | Cardiac disorders | Systematic Assessment |
|
| Urinary tract infection | Renal and urinary disorders | Systematic Assessment |
|
| Diarrhea | Metabolism and nutrition disorders | Systematic Assessment |
|
| Dark and Infrequent Urination | Renal and urinary disorders | Systematic Assessment |
|
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| D014777 |
| Virus Diseases |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| 5 |
|
| 6 |
|
| 7 |
|
| 8 |
|
| 9 |
|
| 10 |
|
| WHO Clinical Status: Day 7 |
|
| WHO Clinical Status: Day 14 |
|