CRITICAL: Crizanlizumab for Treating COVID-19 Vasculopathy

• Sponsor: Johns Hopkins University (Other)
• Overall Status: Completed
• CT.gov ID: NCT04435184
• Collaborator: Novartis (Industry), Socar Research SA (Other), Brigham and Women's Hospital (Other)
• Enrollment: 54
• Location: 1
• Arms: 2
• Actual Duration (Months): 5.9
• Patients Per Site Per Month: 9.2

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
COVID-19	Drug: Crizanlizumab; Other: 0.9% saline	Phase 2

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 54 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Double-blind, placebo-controlled, randomized interventional trial.Double-blind, placebo-controlled, randomized interventional trial.
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Crizanlizumab for Treating COVID-19 Vasculopathy
• Actual Study Start Date: Jul 9, 2020
• Actual Primary Completion Date: Nov 28, 2020
• Actual Study Completion Date: Jan 4, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Crizanlizumab Crizanlizumab is a monoclonal antibody targeting P-selectin. Crizanlizumab 5.0 mg/kg in 100 ml IV once.	Drug: Crizanlizumab; Crizanlizumab 5.0 mg/kg in 100 ml IV once.
Active Comparator: Placebo Saline 0.9% saline 100 ml IV once.	Other: 0.9% saline; 0.9% saline 100 ml IV once.

Outcome Measures

Primary Outcome Measures

1. Soluble P-selectin Level [Day 3 after randomization or day of hospital discharge, whichever is earlier]

   Level of soluble P-selectin in ng/mL.

Secondary Outcome Measures

1. Soluble P-selectin Level [Day 7 after randomization]

   Level of soluble P-selectin in ng/mL.

2. Soluble P-selectin Level [Day 14 after randomization]

   Level of soluble P-selectin in ng/mL.

3. D-dimer Level [Day 3 after randomization]

   Level of D-dimer in mg/L.

4. D-dimer Level [Day 7 after randomization]

   Level of D-dimer in mg/L.

5. D-dimer Level [Day 14 after randomization]

   Level of D-dimer in mg/L.

6. VWF Level [Day 3 after randomization]

   Level of von Willebrand Factor (VWF) antigen in IU/mL.

7. VWF Level [Day 7 after randomization]

   Level of VWF antigen in IU/mL.

8. VWF Level [Day 14 after randomization]

   Level of VWF antigen in IU/mL.

9. CRP Level [Day 3 after randomization]

   Level of C-reactive protein (CRP) in mg/dL.

10. CRP Level [Day 7 after randomization]

    Level of C-reactive protein (CRP) in mg/dL.

11. CRP Level [Day 14 after randomization]

    Level of C-reactive protein (CRP) in mg/dL.

12. Change in Clinical Status as Assessed by the World Health Organization (WHO) Ordinal Scale for Coronavirus Disease 2019 (COVID-19) Trials [Days 3, 7 and 14 after randomization]

    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

13. Time to Hospital Discharge [Up to 30 days after randomization]

    Time (days) to hospital discharge

14. Safety of Crizanlizumab as Assessed by Adverse Events [Up to day 14 after randomization]

    Safety of crizanlizumab will by assessed by adverse events, serious adverse events, and suspected unexpected serious adverse reactions.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Johns Hopkins Hospital	Baltimore	Maryland	United States	21287

Sponsors and Collaborators

• Johns Hopkins University
• Novartis
• Socar Research SA
• Brigham and Women's Hospital

Investigators

• Principal Investigator: Charles J Lowenstein, MD, Johns Hopkins University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 14, 2020

More Information

Publications

• 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.

• Responsible Party: Johns Hopkins University
• ClinicalTrials.gov Identifier: NCT04435184
• Other Study ID Numbers: IRB00249874
• First Posted: Jun 17, 2020
• Last Update Posted: Nov 9, 2021
• Last Verified: Nov 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Johns Hopkins University: coronavirus
• Additional relevant MeSH terms: COVID-19

Study Results

Participant Flow

Recruitment Details	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).
Pre-assignment Detail	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.

Arm/Group Title	Crizanlizumab	Placebo Saline
Arm/Group Description	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.	0.9% saline 100 ml IV once. 0.9% saline: 0.9% saline 100 ml IV once.
Period Title: Overall Study
STARTED	25	25
COMPLETED	22	20
NOT COMPLETED	3	5

Baseline Characteristics

Arm/Group Title	Crizanlizumab	Placebo Saline	Total
Arm/Group Description	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.	0.9% saline 100 ml IV once. 0.9% saline: 0.9% saline 100 ml IV once.	Total of all reporting groups
Overall Participants	22	20	42
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	19 86.4%	12 60%	31 73.8%
>=65 years	3 13.6%	8 40%	11 26.2%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58 (17.7)	54.6 (13.4)	56.2 (15.5)
Sex: Female, Male (Count of Participants)
Female	9 40.9%	9 45%	18 42.9%
Male	13 59.1%	11 55%	24 57.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	1 5%	1 2.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	14 63.6%	6 30%	20 47.6%
White	8 36.4%	13 65%	21 50%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	22 100%	20 100%	42 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Crizanlizumab	Placebo Saline
Arm/Group Description	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.	0.9% saline 100 ml IV once. 0.9% saline: 0.9% saline 100 ml IV once.
Measure Participants	22	20
Mean (Standard Deviation) [ng/mL]	7 (7)	39 (18)

2. Secondary Outcome

Title	Soluble P-selectin Level
Description	Level of soluble P-selectin in ng/mL.
Time Frame	Day 7 after randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Crizanlizumab	Placebo Saline
Arm/Group Description	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.	0.9% saline 100 ml IV once. 0.9% saline: 0.9% saline 100 ml IV once.
Measure Participants	22	20
Mean (Standard Deviation) [ng/mL]	10 (8)	48 (17)

3. Secondary Outcome

Title	Soluble P-selectin Level
Description	Level of soluble P-selectin in ng/mL.
Time Frame	Day 14 after randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Crizanlizumab	Placebo Saline
Arm/Group Description	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.	0.9% saline 100 ml IV once. 0.9% saline: 0.9% saline 100 ml IV once.
Measure Participants	22	20
Mean (Standard Deviation) [ng/mL]	12 (10)	48 (24)

4. Secondary Outcome

Title	D-dimer Level
Description	Level of D-dimer in mg/L.
Time Frame	Day 3 after randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Crizanlizumab	Placebo Saline
Arm/Group Description	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.	0.9% saline 100 ml IV once. 0.9% saline: 0.9% saline 100 ml IV once.
Measure Participants	22	20
Median (Inter-Quartile Range) [mg/L]	1.6	0.7

5. Secondary Outcome

Title	D-dimer Level
Description	Level of D-dimer in mg/L.
Time Frame	Day 7 after randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Crizanlizumab	Placebo Saline
Arm/Group Description	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.	0.9% saline 100 ml IV once. 0.9% saline: 0.9% saline 100 ml IV once.
Measure Participants	22	20
Median (Inter-Quartile Range) [mg/L]	1.6	0.7

6. Secondary Outcome

Title	D-dimer Level
Description	Level of D-dimer in mg/L.
Time Frame	Day 14 after randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Crizanlizumab	Placebo Saline
Arm/Group Description	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.	0.9% saline 100 ml IV once. 0.9% saline: 0.9% saline 100 ml IV once.
Measure Participants	22	20
Median (Inter-Quartile Range) [mg/L]	1.5	0.7

7. Secondary Outcome

Title	VWF Level
Description	Level of von Willebrand Factor (VWF) antigen in IU/mL.
Time Frame	Day 3 after randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Crizanlizumab	Placebo Saline
Arm/Group Description	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.	0.9% saline 100 ml IV once. 0.9% saline: 0.9% saline 100 ml IV once.
Measure Participants	22	20
Median (Inter-Quartile Range) [IU/mL]	2.9	2.8

8. Secondary Outcome

Title	VWF Level
Description	Level of VWF antigen in IU/mL.
Time Frame	Day 7 after randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Crizanlizumab	Placebo Saline
Arm/Group Description	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.	0.9% saline 100 ml IV once. 0.9% saline: 0.9% saline 100 ml IV once.
Measure Participants	22	20
Median (Inter-Quartile Range) [IU/mL]	3.9	3.6

9. Secondary Outcome

Title	VWF Level
Description	Level of VWF antigen in IU/mL.
Time Frame	Day 14 after randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Crizanlizumab	Placebo Saline
Arm/Group Description	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.	0.9% saline 100 ml IV once. 0.9% saline: 0.9% saline 100 ml IV once.
Measure Participants	22	20
Median (Inter-Quartile Range) [IU/mL]	2.7	4.6

10. Secondary Outcome

Title	CRP Level
Description	Level of C-reactive protein (CRP) in mg/dL.
Time Frame	Day 3 after randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Crizanlizumab	Placebo Saline
Arm/Group Description	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.	0.9% saline 100 ml IV once. 0.9% saline: 0.9% saline 100 ml IV once.
Measure Participants	22	20
Median (Inter-Quartile Range) [mg/dL]	4.4	4.5

11. Secondary Outcome

Title	CRP Level
Description	Level of C-reactive protein (CRP) in mg/dL.
Time Frame	Day 7 after randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Crizanlizumab	Placebo Saline
Arm/Group Description	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.	0.9% saline 100 ml IV once. 0.9% saline: 0.9% saline 100 ml IV once.
Measure Participants	22	20
Median (Inter-Quartile Range) [mg/dL]	2.4	2.1

12. Secondary Outcome

Title	CRP Level
Description	Level of C-reactive protein (CRP) in mg/dL.
Time Frame	Day 14 after randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Crizanlizumab	Placebo Saline
Arm/Group Description	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.	0.9% saline 100 ml IV once. 0.9% saline: 0.9% saline 100 ml IV once.
Measure Participants	22	20
Median (Inter-Quartile Range) [mg/dL]	2.5	1.3

13. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Crizanlizumab	Placebo Saline
Arm/Group Description	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.	0.9% saline 100 ml IV once. 0.9% saline: 0.9% saline 100 ml IV once.
Measure Participants	22	20
</= 3 (discharged)	3 13.6%	2 10%
4	3 13.6%	7 35%
5	13 59.1%	7 35%
6	3 13.6%	4 20%
7	0 0%	0 0%
8	0 0%	0 0%
9	0 0%	0 0%
10	0 0%	0 0%
</= 3 (discharged)	9 40.9%	13 65%
4	5 22.7%	3 15%
5	6 27.3%	3 15%
6	1 4.5%	1 5%
7	1 4.5%	0 0%
8	0 0%	0 0%
9	0 0%	0 0%
10	0 0%	0 0%
</= 3 (discharged)	21 95.5%	19 95%
4	0 0%	0 0%
5	0 0%	0 0%
6	1 4.5%	0 0%
7	0 0%	0 0%
8	0 0%	1 5%
9	0 0%	0 0%
10	0 0%	0 0%

14. Secondary Outcome

Title	Time to Hospital Discharge
Description	Time (days) to hospital discharge
Time Frame	Up to 30 days after randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Crizanlizumab	Placebo Saline
Arm/Group Description	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.	0.9% saline 100 ml IV once. 0.9% saline: 0.9% saline 100 ml IV once.
Measure Participants	22	20
Mean (Standard Deviation) [days]	8.1 (4.4)	6.2 (3.2)

15. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Crizanlizumab	Placebo Saline
Arm/Group Description	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.	0.9% saline 100 ml IV once. 0.9% saline: 0.9% saline 100 ml IV once.
Measure Participants	25	25
Number [total adverse events]	7	6

Adverse Events

Time Frame	30 days
Arm/Group Title	Crizanlizumab		Placebo Saline
Arm/Group Description	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.		0.9% saline 100 ml IV once. 0.9% saline: 0.9% saline 100 ml IV once.
All Cause Mortality
	Crizanlizumab		Placebo Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/25 (0%)		0/25 (0%)
Serious Adverse Events
	Crizanlizumab		Placebo Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/25 (0%)		1/25 (4%)
General disorders
multi-organ failure	0/25 (0%)	0	1/25 (4%)	1
Other (Not Including Serious) Adverse Events
	Crizanlizumab		Placebo Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/25 (28%)		5/25 (20%)
Cardiac disorders
Chest pain	2/25 (8%)	2	1/25 (4%)	1
Metabolism and nutrition disorders
Diarrhea	1/25 (4%)	1	2/25 (8%)	2
Nervous system disorders
Headache	1/25 (4%)	1	0/25 (0%)	0
Altered mental status	1/25 (4%)	1	0/25 (0%)	0
Renal and urinary disorders
Urinary tract infection	0/25 (0%)	0	1/25 (4%)	1
Dark and Infrequent Urination	1/25 (4%)	1	0/25 (0%)	0
Vascular disorders
Venous thrombembolism	1/25 (4%)	1	1/25 (4%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.