Trial Outcomes & Findings for Crizanlizumab for Treating COVID-19 Vasculopathy (NCT NCT04435184)

NCT ID: NCT04435184

Last Updated: 2021-11-09

Results Overview

Level of soluble P-selectin in ng/mL.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 54 participants
• Primary outcome timeframe: Day 3 after randomization or day of hospital discharge, whichever is earlier
• Results posted on: 2021-11-09

Participant Flow

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).

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 Out of the 27 assigned to receive placebo, 2 did not receive placebo because of early discharge or withdrawn consent.

Participant milestones

Measure	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.	Placebo Saline 0.9% saline 100 ml IV once. 0.9% saline: 0.9% saline 100 ml IV once.
Overall Study STARTED	25	25
Overall Study COMPLETED	22	20
Overall Study NOT COMPLETED	3	5

Reasons for withdrawal

Measure	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.	Placebo Saline 0.9% saline 100 ml IV once. 0.9% saline: 0.9% saline 100 ml IV once.
Overall Study follow-up blood draws missing	3	5

Baseline Characteristics

Crizanlizumab for Treating COVID-19 Vasculopathy

Baseline characteristics by cohort

Measure	Crizanlizumab n=22 Participants 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.	Placebo Saline n=20 Participants 0.9% saline 100 ml IV once. 0.9% saline: 0.9% saline 100 ml IV once.	Total n=42 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	19 Participants n=5 Participants	12 Participants n=7 Participants	31 Participants n=5 Participants
Age, Categorical >=65 years	3 Participants n=5 Participants	8 Participants n=7 Participants	11 Participants n=5 Participants
Age, Continuous	58 years STANDARD_DEVIATION 17.7 • n=5 Participants	54.6 years STANDARD_DEVIATION 13.4 • n=7 Participants	56.2 years STANDARD_DEVIATION 15.5 • n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	9 Participants n=7 Participants	18 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	11 Participants n=7 Participants	24 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	14 Participants n=5 Participants	6 Participants n=7 Participants	20 Participants n=5 Participants
Race (NIH/OMB) White	8 Participants n=5 Participants	13 Participants n=7 Participants	21 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	22 Participants n=5 Participants	20 Participants n=7 Participants	42 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 3 after randomization or day of hospital discharge, whichever is earlier

Level of soluble P-selectin in ng/mL.

Outcome measures

Measure	Crizanlizumab n=22 Participants 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.	Placebo Saline n=20 Participants 0.9% saline 100 ml IV once. 0.9% saline: 0.9% saline 100 ml IV once.
Soluble P-selectin Level	7 ng/mL Standard Deviation 7	39 ng/mL Standard Deviation 18

SECONDARY outcome

Timeframe: Day 7 after randomization

Level of soluble P-selectin in ng/mL.

Outcome measures

Measure	Crizanlizumab n=22 Participants 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.	Placebo Saline n=20 Participants 0.9% saline 100 ml IV once. 0.9% saline: 0.9% saline 100 ml IV once.
Soluble P-selectin Level	10 ng/mL Standard Deviation 8	48 ng/mL Standard Deviation 17

SECONDARY outcome

Timeframe: Day 14 after randomization

Level of soluble P-selectin in ng/mL.

Outcome measures

Measure	Crizanlizumab n=22 Participants 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.	Placebo Saline n=20 Participants 0.9% saline 100 ml IV once. 0.9% saline: 0.9% saline 100 ml IV once.
Soluble P-selectin Level	12 ng/mL Standard Deviation 10	48 ng/mL Standard Deviation 24

SECONDARY outcome

Timeframe: Day 3 after randomization

Level of D-dimer in mg/L.

Outcome measures

Measure	Crizanlizumab n=22 Participants 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.	Placebo Saline n=20 Participants 0.9% saline 100 ml IV once. 0.9% saline: 0.9% saline 100 ml IV once.
D-dimer Level	1.6 mg/L Interval 0.7 to 2.8	0.7 mg/L Interval 0.5 to 1.4

SECONDARY outcome

Timeframe: Day 7 after randomization

Level of D-dimer in mg/L.

Outcome measures

Measure	Crizanlizumab n=22 Participants 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.	Placebo Saline n=20 Participants 0.9% saline 100 ml IV once. 0.9% saline: 0.9% saline 100 ml IV once.
D-dimer Level	1.6 mg/L Interval 0.6 to 2.0	0.7 mg/L Interval 0.5 to 0.8

SECONDARY outcome

Timeframe: Day 14 after randomization

Level of D-dimer in mg/L.

Outcome measures

Measure	Crizanlizumab n=22 Participants 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.	Placebo Saline n=20 Participants 0.9% saline 100 ml IV once. 0.9% saline: 0.9% saline 100 ml IV once.
D-dimer Level	1.5 mg/L Interval 0.5 to 1.9	0.7 mg/L Interval 0.5 to 0.8

SECONDARY outcome

Timeframe: Day 3 after randomization

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

Outcome measures

Measure	Crizanlizumab n=22 Participants 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.	Placebo Saline n=20 Participants 0.9% saline 100 ml IV once. 0.9% saline: 0.9% saline 100 ml IV once.
VWF Level	2.9 IU/mL Interval 1.9 to 4.9	2.8 IU/mL Interval 1.7 to 4.1

SECONDARY outcome

Timeframe: Day 7 after randomization

Level of VWF antigen in IU/mL.

Outcome measures

Measure	Crizanlizumab n=22 Participants 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.	Placebo Saline n=20 Participants 0.9% saline 100 ml IV once. 0.9% saline: 0.9% saline 100 ml IV once.
VWF Level	3.9 IU/mL Interval 2.5 to 5.9	3.6 IU/mL Interval 2.1 to 6.8

SECONDARY outcome

Timeframe: Day 14 after randomization

Level of VWF antigen in IU/mL.

Outcome measures

Measure	Crizanlizumab n=22 Participants 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.	Placebo Saline n=20 Participants 0.9% saline 100 ml IV once. 0.9% saline: 0.9% saline 100 ml IV once.
VWF Level	2.7 IU/mL Interval 1.9 to 4.2	4.6 IU/mL Interval 2.6 to 7.4

SECONDARY outcome

Timeframe: Day 3 after randomization

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

Outcome measures

Measure	Crizanlizumab n=22 Participants 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.	Placebo Saline n=20 Participants 0.9% saline 100 ml IV once. 0.9% saline: 0.9% saline 100 ml IV once.
CRP Level	4.4 mg/dL Interval 2.1 to 5.6	4.5 mg/dL Interval 1.2 to 6.9

SECONDARY outcome

Timeframe: Day 7 after randomization

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

Outcome measures

Measure	Crizanlizumab n=22 Participants 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.	Placebo Saline n=20 Participants 0.9% saline 100 ml IV once. 0.9% saline: 0.9% saline 100 ml IV once.
CRP Level	2.4 mg/dL Interval 1.1 to 4.9	2.1 mg/dL Interval 0.6 to 4.2

SECONDARY outcome

Timeframe: Day 14 after randomization

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

Outcome measures

Measure	Crizanlizumab n=22 Participants 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.	Placebo Saline n=20 Participants 0.9% saline 100 ml IV once. 0.9% saline: 0.9% saline 100 ml IV once.
CRP Level	2.5 mg/dL Interval 1.1 to 5.1	1.3 mg/dL Interval 0.6 to 4.9

SECONDARY outcome

Timeframe: 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

1. = Ambulatory; asymptomatic; viral RNA detected

2. = Ambulatory; symptomatic; independent

3. = Ambulatory; symptomatic; assistance needed

4. = Hospitalized; no oxygen therapy

5. = Hospitalized; oxygen by mask or nasal prongs

6. = Hospitalized; oxygen by non-invasive ventilation (NIV) or high flow

7. = Hospitalized; intubation and mechanical ventilation, partial pressure of oxygen / fraction of inspired oxygen (pO2/FIO2) ≥ 150 or oxygen saturation / FIO2 (SpO2/FIO2) ≥ 200

8. = Hospitalized; intubation and mechanical ventilation, pO2/FIO2 < 150 or SpO2/FIO2 < 200 or vasopressors

9. = Hospitalized; intubation and mechanical ventilation, pO2/FIO2 < 150 or SpO2/FIO2 < 200 and vasopressors, dialysis, or extracorporeal membrane oxygenation (ECMO)

10. = Dead

Outcome measures

Measure	Crizanlizumab n=22 Participants 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.	Placebo Saline n=20 Participants 0.9% saline 100 ml IV once. 0.9% saline: 0.9% saline 100 ml IV once.
Change in Clinical Status as Assessed by the World Health Organization (WHO) Ordinal Scale for Coronavirus Disease 2019 (COVID-19) Trials WHO Clinical Status: Day 3 · </= 3 (discharged)	3 Participants	2 Participants
Change in Clinical Status as Assessed by the World Health Organization (WHO) Ordinal Scale for Coronavirus Disease 2019 (COVID-19) Trials WHO Clinical Status: Day 3 · 10	0 Participants	0 Participants
Change in Clinical Status as Assessed by the World Health Organization (WHO) Ordinal Scale for Coronavirus Disease 2019 (COVID-19) Trials WHO Clinical Status: Day 7 · </= 3 (discharged)	9 Participants	13 Participants
Change in Clinical Status as Assessed by the World Health Organization (WHO) Ordinal Scale for Coronavirus Disease 2019 (COVID-19) Trials WHO Clinical Status: Day 7 · 9	0 Participants	0 Participants
Change in Clinical Status as Assessed by the World Health Organization (WHO) Ordinal Scale for Coronavirus Disease 2019 (COVID-19) Trials WHO Clinical Status: Day 3 · 4	3 Participants	7 Participants
Change in Clinical Status as Assessed by the World Health Organization (WHO) Ordinal Scale for Coronavirus Disease 2019 (COVID-19) Trials WHO Clinical Status: Day 3 · 5	13 Participants	7 Participants
Change in Clinical Status as Assessed by the World Health Organization (WHO) Ordinal Scale for Coronavirus Disease 2019 (COVID-19) Trials WHO Clinical Status: Day 3 · 6	3 Participants	4 Participants
Change in Clinical Status as Assessed by the World Health Organization (WHO) Ordinal Scale for Coronavirus Disease 2019 (COVID-19) Trials WHO Clinical Status: Day 3 · 7	0 Participants	0 Participants
Change in Clinical Status as Assessed by the World Health Organization (WHO) Ordinal Scale for Coronavirus Disease 2019 (COVID-19) Trials WHO Clinical Status: Day 3 · 8	0 Participants	0 Participants
Change in Clinical Status as Assessed by the World Health Organization (WHO) Ordinal Scale for Coronavirus Disease 2019 (COVID-19) Trials WHO Clinical Status: Day 3 · 9	0 Participants	0 Participants
Change in Clinical Status as Assessed by the World Health Organization (WHO) Ordinal Scale for Coronavirus Disease 2019 (COVID-19) Trials WHO Clinical Status: Day 7 · 4	5 Participants	3 Participants
Change in Clinical Status as Assessed by the World Health Organization (WHO) Ordinal Scale for Coronavirus Disease 2019 (COVID-19) Trials WHO Clinical Status: Day 7 · 5	6 Participants	3 Participants
Change in Clinical Status as Assessed by the World Health Organization (WHO) Ordinal Scale for Coronavirus Disease 2019 (COVID-19) Trials WHO Clinical Status: Day 7 · 6	1 Participants	1 Participants
Change in Clinical Status as Assessed by the World Health Organization (WHO) Ordinal Scale for Coronavirus Disease 2019 (COVID-19) Trials WHO Clinical Status: Day 7 · 7	1 Participants	0 Participants
Change in Clinical Status as Assessed by the World Health Organization (WHO) Ordinal Scale for Coronavirus Disease 2019 (COVID-19) Trials WHO Clinical Status: Day 7 · 8	0 Participants	0 Participants
Change in Clinical Status as Assessed by the World Health Organization (WHO) Ordinal Scale for Coronavirus Disease 2019 (COVID-19) Trials WHO Clinical Status: Day 7 · 10	0 Participants	0 Participants
Change in Clinical Status as Assessed by the World Health Organization (WHO) Ordinal Scale for Coronavirus Disease 2019 (COVID-19) Trials WHO Clinical Status: Day 14 · </= 3 (discharged)	21 Participants	19 Participants
Change in Clinical Status as Assessed by the World Health Organization (WHO) Ordinal Scale for Coronavirus Disease 2019 (COVID-19) Trials WHO Clinical Status: Day 14 · 4	0 Participants	0 Participants
Change in Clinical Status as Assessed by the World Health Organization (WHO) Ordinal Scale for Coronavirus Disease 2019 (COVID-19) Trials WHO Clinical Status: Day 14 · 5	0 Participants	0 Participants
Change in Clinical Status as Assessed by the World Health Organization (WHO) Ordinal Scale for Coronavirus Disease 2019 (COVID-19) Trials WHO Clinical Status: Day 14 · 6	1 Participants	0 Participants
Change in Clinical Status as Assessed by the World Health Organization (WHO) Ordinal Scale for Coronavirus Disease 2019 (COVID-19) Trials WHO Clinical Status: Day 14 · 7	0 Participants	0 Participants
Change in Clinical Status as Assessed by the World Health Organization (WHO) Ordinal Scale for Coronavirus Disease 2019 (COVID-19) Trials WHO Clinical Status: Day 14 · 8	0 Participants	1 Participants
Change in Clinical Status as Assessed by the World Health Organization (WHO) Ordinal Scale for Coronavirus Disease 2019 (COVID-19) Trials WHO Clinical Status: Day 14 · 9	0 Participants	0 Participants
Change in Clinical Status as Assessed by the World Health Organization (WHO) Ordinal Scale for Coronavirus Disease 2019 (COVID-19) Trials WHO Clinical Status: Day 14 · 10	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 30 days after randomization

Time (days) to hospital discharge

Outcome measures

Measure	Crizanlizumab n=22 Participants 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.	Placebo Saline n=20 Participants 0.9% saline 100 ml IV once. 0.9% saline: 0.9% saline 100 ml IV once.
Time to Hospital Discharge	8.1 days Standard Deviation 4.4	6.2 days Standard Deviation 3.2

SECONDARY outcome

Timeframe: Up to day 14 after randomization

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

Outcome measures

Measure	Crizanlizumab n=25 Participants 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.	Placebo Saline n=25 Participants 0.9% saline 100 ml IV once. 0.9% saline: 0.9% saline 100 ml IV once.
Safety of Crizanlizumab as Assessed by Adverse Events	7 total adverse events	6 total adverse events

Adverse Events

Crizanlizumab

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Placebo Saline

Serious events: 1 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Measure	Crizanlizumab n=25 participants at risk 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.	Placebo Saline n=25 participants at risk 0.9% saline 100 ml IV once. 0.9% saline: 0.9% saline 100 ml IV once.
General disorders multi-organ failure	0.00% 0/25 • 30 days	4.0% 1/25 • Number of events 1 • 30 days

Other adverse events

Measure	Crizanlizumab n=25 participants at risk 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.	Placebo Saline n=25 participants at risk 0.9% saline 100 ml IV once. 0.9% saline: 0.9% saline 100 ml IV once.
Nervous system disorders Headache	4.0% 1/25 • Number of events 1 • 30 days	0.00% 0/25 • 30 days
Vascular disorders Venous thrombembolism	4.0% 1/25 • Number of events 1 • 30 days	4.0% 1/25 • Number of events 1 • 30 days
Nervous system disorders Altered mental status	4.0% 1/25 • Number of events 1 • 30 days	0.00% 0/25 • 30 days
Cardiac disorders Chest pain	8.0% 2/25 • Number of events 2 • 30 days	4.0% 1/25 • Number of events 1 • 30 days
Renal and urinary disorders Urinary tract infection	0.00% 0/25 • 30 days	4.0% 1/25 • Number of events 1 • 30 days
Metabolism and nutrition disorders Diarrhea	4.0% 1/25 • Number of events 1 • 30 days	8.0% 2/25 • Number of events 2 • 30 days
Renal and urinary disorders Dark and Infrequent Urination	4.0% 1/25 • Number of events 1 • 30 days	0.00% 0/25 • 30 days

Additional Information

Dr. Charles Lowenstein

Johns Hopkins University - Baltimore, MD

Phone: 4105020391

Email: clowens1@jhmi.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place