Treatment With CSL312 in Adults With Coronavirus Disease 2019 (COVID-19)
Study Details
Study Description
Brief Summary
This is a prospective, phase 2, multicenter, randomized, double blind, placebo controlled, parallel group study to assess the safety and efficacy of CSL312 administered intravenously, in combination with standard of care (SOC) treatment, in patients with Coronavirus disease 2019 (COVID 19)
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: CSL312 Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously |
Biological: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody
Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously
|
Placebo Comparator: Placebo CSL312 diluent administered intravenously |
Drug: Placebo
CSL312 diluent administered intravenously
|
Outcome Measures
Primary Outcome Measures
- The Percent of Participants With Tracheal Intubation or Death Prior to Tracheal Intubation [From randomization to Day 28]
Secondary Outcome Measures
- Percent of Participants With Death From All Causes [From randomization to Day 28]
- Percent of Participants With Tracheal Intubation [From randomization to Day 28]
- Number of Participants With ≥ 2-Point Improvement Compared to Baseline on National Institute of Allergy and Infectious Diseases (NIAID) Ordinal Scale [From randomization to Day 28]
The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.
- Percent of Participants With ≥ 2-Point Improvement Compared to Baseline on NIAID [From randomization to Day 28]
The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.
- Number of Participants Within Each of the Categories of the NIAID at End of Study [Day 28]
The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.
- Percent of Participants Within Each of the Categories of the NIAID at End of Study [Day 28]
The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.
- Percent of Participants Requiring Continuous Positive Airway Pressure (CPAP) or Bilevel Positive Airway Pressure (BiPAP) [From randomization to Day 28]
- Percent of Participants Requiring Extracorporeal Membrane Oxygenation (ECMO) [From randomization to Day 28]
None of the enrolled subjects required the use of ECMO during their participation in this study. Therefore, no data to report for this outcome measure.
- Percent of Participants Requiring High-Flow Nasal Cannula (HFNC) [From randomization to Day 28]
- Maximum Change From Baseline in Sequential Organ Failure Assessment (SOFA) Score [From randomization to Day 28]
The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems. Each system is scored from 0 (normal function) to 4 (most abnormal) with a total score ranging from 0 to 24. A high total SOFA score have been shown to be related to a worse outcome.
- Change From Baseline in SOFA Total Score [From randomization to Day 28]
The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems. Each system is scored from 0 (normal function) to 4 (most abnormal) with a total score ranging from 0 to 24. A high total SOFA score have been shown to be related to a worse outcome.
- Change From Baseline in the Individual Components of SOFA Score [From randomization to Day 28]
The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems. Each system is scored from 0 (normal function) to 4 (most abnormal) with a total score ranging from 0 to 24. A high total SOFA score have been shown to be related to a worse outcome.
- Length of Hospital Stay [From randomization to Day 28 (+/- 2 days)]
- Number of Participants Experiencing Adverse Events (AEs) [Up to 28 days after CSL312 or placebo administration]
- Percent of Participants Experiencing AEs [Up to 28 days after CSL312 or placebo administration]
- Number of Participants Experiencing Serious Adverse Events (SAEs) [Up to 28 days after CSL312 or placebo administration]
- Percent of Participants Experiencing SAEs [Up to 28 days after CSL312 or placebo administration]
- Number of Participants With Adverse Events of Special Interest (AESIs) [Up to 28 days after CSL312 or placebo administration]
- Percent of Participants With AESIs [Up to 28 days after CSL312 or placebo administration]
- Number of Participants With Anti-CSL312 Antibodies [Up to 28 days after CSL312 or placebo administration]
- Maximum Plasma Concentration (Cmax) of CSL312 [Up to 28 days after CSL312 administration]
- Time to Maximum Plasma Concentration (Tmax) of CSL312 [Up to 28 days after CSL312 administration]
- Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Measurable Concentration (AUC0-Last) of CSL312 [Up to 28 days after CSL312 administration]
- Terminal Half-life (T1/2) of CSL312 [Up to 28 days after CSL312 administration]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Age ≥ 18 years
-
Positive for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection as determined using a molecular diagnostic test (reverse transcription polymerase chain reaction [RT-PCR] or equivalent) approved by regulatory authorities (including Food and Drug Administration or Brazilian Health Regulatory Agency) or allowed under an emergency use authorization within 14 days before Screening. If a false negative result is suspected, the SARS-CoV-2 test may be repeated within the Screening Period.
-
Chest CT scan or X ray results confirming interstitial pneumonia
-
Severe COVID 19 disease as evidenced by ≥ 1 of the following criteria at Screening including within 24 hours before Screening:
-
Respiratory frequency > 30 breaths per minute
-
SpO2 ≤ 93% on room air
-
Ratio of partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2/FiO2) < 300
-
Ratio of Arterial oxygen saturation to fraction of inspired oxygen (SaO2/FiO2 ratio) < 218 (if PaO2/FiO2 ratio is not available)
-
Radiographic lung infiltrates > 50%
Exclusion Criteria:
-
Currently enrolled, planning to enroll, or participated, within the last 30 days, in a clinical study requiring administration of an IP, including expanded access or compassionate use with the only exception being administration of convalescent plasma. Administration of IP is permitted only if an emergency use authorization has been granted (eg, remdesivir). Additionally, off label use of approved drugs (eg, anti IL 6/anti IL 6R) is also permitted.
-
Pregnant or breastfeeding (female subjects)
-
Intubated and require mechanical ventilation (including ECMO) at the time of randomization
-
In the opinion of the investigator, the subject is expected to be intubated in the first 24 hours after IMP administration
-
Has a Do-Not-Intubate (DNI) or Do-Not-Resuscitate (DNR) order
-
In the opinion of the investigator, not expected to survive for > 48 hours after admission
-
Presence of any of the following comorbid conditions prior to randomization and prior to SARS CoV 2 infection:
-
Severe heart failure (New York Heart Association Class IV)
-
End stage renal disease (Stage ≥ 4) or need for renal replacement therapy
-
Biopsy confirmed cirrhosis, portal hypertension, or hepatic encephalopathy
-
Malignancy (Stage IV)
-
Chronic lung disease requiring the use of oxygen at home
-
Active tuberculosis disease
-
Active bleeding or a current clinically significant coagulopathy (eg, international normalized ratio [INR] > 1.5) or clinically significant risk for bleeding (eg, recent intracranial hemorrhage or bleeding peptic ulcer within the last 4 weeks)
-
History of venous thrombosis, myocardial infarction or cerebrovascular event within 3 months, or a prothrombotic disorder (eg, antithrombin III, protein C or protein S deficiency)
-
Known or suspected Grade 3 or 4 infusion-related reaction or hypersensitivity (per Common Terminology Criteria for Adverse Events [CTCAE]) to monoclonal antibody therapy, or hypersensitivity to the IMP or any excipients of the IMP
-
Currently receiving a therapy not permitted during the study.
-
Female subject of childbearing potential or fertile male subject either not using or not willing to use an acceptable method of contraception to avoid pregnancy during the study and for 90 days after receipt of the last dose of IMP
-
Any clinical or laboratory abnormality or other underlying conditions (eg, psychological disorders, substance abuse) that would render the subject unsuitable for participation in the study, in the opinion of the investigator
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Nova Clinical Research, LLC | Bradenton | Florida | United States | 34209 |
2 | Theia Clinical Research, LLC | Saint Petersburg | Florida | United States | 33707 |
3 | MercyOne North Iowa Medical Center | Mason City | Iowa | United States | 50401 |
4 | Northeast Iowa Medical Education Foundation | Waterloo | Iowa | United States | 50702 |
5 | Lahey Hospital and Medical Center | Burlington | Massachusetts | United States | 01805 |
6 | University of Mississippi Medical Center | Jackson | Mississippi | United States | 39216 |
7 | Holy Name Hospital | Teaneck | New Jersey | United States | 07666 |
8 | Inspira Health Center Vineland | Vineland | New Jersey | United States | 08360 |
9 | Sisters of Charity Hospital/ St. Joseph's Campus | Buffalo | New York | United States | 14225 |
10 | Carolina Institute for Clinical Research | Fayetteville | North Carolina | United States | 28304 |
11 | Monument Health Clinical Research | Rapid City | South Dakota | United States | 57701 |
12 | PharmaTex Research | Amarillo | Texas | United States | 79109 |
13 | UT Health Science Center, McGovern Medical School | Houston | Texas | United States | 77030 |
14 | Inova Alexandria Hospital | Alexandria | Virginia | United States | 22304 |
Sponsors and Collaborators
- CSL Behring
Investigators
- Study Director: Study Director, CSL Behring
Study Documents (Full-Text)
More Information
Publications
None provided.- CSL312_COVID-19
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | Placebo | CSL312 |
---|---|---|
Arm/Group Description | CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously | Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously |
Period Title: Overall Study | ||
STARTED | 61 | 63 |
COMPLETED | 48 | 43 |
NOT COMPLETED | 13 | 20 |
Baseline Characteristics
Arm/Group Title | Placebo | CSL312 | Total |
---|---|---|---|
Arm/Group Description | CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously | Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously | Total of all reporting groups |
Overall Participants | 61 | 63 | 124 |
Age (Count of Participants) | |||
<=18 years |
0
0%
|
0
0%
|
0
0%
|
Between 18 and 65 years |
33
54.1%
|
32
50.8%
|
65
52.4%
|
>=65 years |
28
45.9%
|
31
49.2%
|
59
47.6%
|
Age (years) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [years] |
62.2
(12.74)
|
62.7
(14.61)
|
62.5
(13.67)
|
Sex: Female, Male (Count of Participants) | |||
Female |
20
32.8%
|
30
47.6%
|
50
40.3%
|
Male |
41
67.2%
|
33
52.4%
|
74
59.7%
|
Ethnicity (NIH/OMB) (Count of Participants) | |||
Hispanic or Latino |
10
16.4%
|
14
22.2%
|
24
19.4%
|
Not Hispanic or Latino |
48
78.7%
|
48
76.2%
|
96
77.4%
|
Unknown or Not Reported |
3
4.9%
|
1
1.6%
|
4
3.2%
|
Race (NIH/OMB) (Count of Participants) | |||
American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
Asian |
2
3.3%
|
2
3.2%
|
4
3.2%
|
Native Hawaiian or Other Pacific Islander |
1
1.6%
|
0
0%
|
1
0.8%
|
Black or African American |
6
9.8%
|
7
11.1%
|
13
10.5%
|
White |
49
80.3%
|
44
69.8%
|
93
75%
|
More than one race |
0
0%
|
1
1.6%
|
1
0.8%
|
Unknown or Not Reported |
3
4.9%
|
9
14.3%
|
12
9.7%
|
Region of Enrollment (participants) [Number] | |||
United States |
61
100%
|
63
100%
|
124
100%
|
Outcome Measures
Title | The Percent of Participants With Tracheal Intubation or Death Prior to Tracheal Intubation |
---|---|
Description | |
Time Frame | From randomization to Day 28 |
Outcome Measure Data
Analysis Population Description |
---|
Intent-to-treat Analysis Set (ITT) comprises all subjects who were randomly assigned to treatment and who were assigned randomization numbers. |
Arm/Group Title | Placebo | CSL312 |
---|---|---|
Arm/Group Description | CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously | Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously |
Measure Participants | 61 | 63 |
Number [percentage of participants] |
26.2
43%
|
22.2
35.2%
|
Title | Percent of Participants With Death From All Causes |
---|---|
Description | |
Time Frame | From randomization to Day 28 |
Outcome Measure Data
Analysis Population Description |
---|
ITT |
Arm/Group Title | Placebo | CSL312 |
---|---|---|
Arm/Group Description | CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously | Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously |
Measure Participants | 61 | 63 |
Number [percentage of participants] |
18.0
29.5%
|
17.5
27.8%
|
Title | Percent of Participants With Tracheal Intubation |
---|---|
Description | |
Time Frame | From randomization to Day 28 |
Outcome Measure Data
Analysis Population Description |
---|
ITT |
Arm/Group Title | Placebo | CSL312 |
---|---|---|
Arm/Group Description | CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously | Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously |
Measure Participants | 61 | 63 |
Number [percentage of participants] |
24.6
40.3%
|
17.5
27.8%
|
Title | Number of Participants With ≥ 2-Point Improvement Compared to Baseline on National Institute of Allergy and Infectious Diseases (NIAID) Ordinal Scale |
---|---|
Description | The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities. |
Time Frame | From randomization to Day 28 |
Outcome Measure Data
Analysis Population Description |
---|
ITT |
Arm/Group Title | Placebo | CSL312 |
---|---|---|
Arm/Group Description | CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously | Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously |
Measure Participants | 61 | 63 |
Number [participants] |
44
72.1%
|
42
66.7%
|
Title | Percent of Participants With ≥ 2-Point Improvement Compared to Baseline on NIAID |
---|---|
Description | The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities. |
Time Frame | From randomization to Day 28 |
Outcome Measure Data
Analysis Population Description |
---|
ITT |
Arm/Group Title | Placebo | CSL312 |
---|---|---|
Arm/Group Description | CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously | Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously |
Measure Participants | 61 | 63 |
Number [percentage of participants] |
72.1
118.2%
|
66.7
105.9%
|
Title | Number of Participants Within Each of the Categories of the NIAID at End of Study |
---|---|
Description | The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities. |
Time Frame | Day 28 |
Outcome Measure Data
Analysis Population Description |
---|
ITT |
Arm/Group Title | Placebo | CSL312 |
---|---|---|
Arm/Group Description | CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously | Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously |
Measure Participants | 61 | 63 |
Death |
11
18%
|
11
17.5%
|
Hospitalized, on Invasive Mechanical Ventilation or ECMO |
2
3.3%
|
1
1.6%
|
Hospitalized, on Non-invasive Ventilation or High-flow Oxygen Devices |
2
3.3%
|
0
0%
|
Hospitalized, Requiring Supplemental Oxygen |
1
1.6%
|
2
3.2%
|
Hospitalized, Not Requiring Supplemental Oxygen - Requiring Ongoing Medical Care |
0
0%
|
0
0%
|
Hospitalized, Not Requiring Supplemental Oxygen - no Longer Requiring Medical Care |
0
0%
|
0
0%
|
Not Hospitalized, Limitation on Activities and/or Requiring Home Oxygen |
14
23%
|
11
17.5%
|
Not Hospitalized, no Limitations on Activities |
25
41%
|
26
41.3%
|
Not Done |
5
8.2%
|
6
9.5%
|
Missing |
1
1.6%
|
6
9.5%
|
Title | Percent of Participants Within Each of the Categories of the NIAID at End of Study |
---|---|
Description | The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities. |
Time Frame | Day 28 |
Outcome Measure Data
Analysis Population Description |
---|
ITT |
Arm/Group Title | Placebo | CSL312 |
---|---|---|
Arm/Group Description | CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously | Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously |
Measure Participants | 61 | 63 |
Death |
18.0
29.5%
|
17.5
27.8%
|
Hospitalized, on Invasive Mechanical Ventilation or ECMO |
3.3
5.4%
|
1.6
2.5%
|
Hospitalized, on Non-invasive Ventilation or High-flow Oxygen Devices |
3.3
5.4%
|
0
0%
|
Hospitalized, Requiring Supplemental Oxygen |
1.6
2.6%
|
3.2
5.1%
|
Hospitalized, Not Requiring Supplemental Oxygen - Requiring Ongoing Medical Care |
0
0%
|
0
0%
|
Hospitalized, Not Requiring Supplemental Oxygen - no Longer Requiring Medical Care |
0
0%
|
0
0%
|
Not Hospitalized, Limitation on Activities and/or Requiring Home Oxygen |
23.0
37.7%
|
17.5
27.8%
|
Not Hospitalized, no Limitations on Activities |
41.0
67.2%
|
41.3
65.6%
|
Not Done |
8.2
13.4%
|
9.5
15.1%
|
Missing |
1.6
2.6%
|
9.5
15.1%
|
Title | Percent of Participants Requiring Continuous Positive Airway Pressure (CPAP) or Bilevel Positive Airway Pressure (BiPAP) |
---|---|
Description | |
Time Frame | From randomization to Day 28 |
Outcome Measure Data
Analysis Population Description |
---|
ITT |
Arm/Group Title | Placebo | CSL312 |
---|---|---|
Arm/Group Description | CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously | Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously |
Measure Participants | 61 | 63 |
Number [percentage of participants] |
16.4
26.9%
|
19.0
30.2%
|
Title | Percent of Participants Requiring Extracorporeal Membrane Oxygenation (ECMO) |
---|---|
Description | None of the enrolled subjects required the use of ECMO during their participation in this study. Therefore, no data to report for this outcome measure. |
Time Frame | From randomization to Day 28 |
Outcome Measure Data
Analysis Population Description |
---|
ITT. None of the enrolled subjects required the use of ECMO during their participation in this study. Therefore, no data to report for this outcome measure. |
Arm/Group Title | Placebo | CSL312 |
---|---|---|
Arm/Group Description | CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously | Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously |
Measure Participants | 61 | 63 |
Number [percentage of participants] |
0
0%
|
0
0%
|
Title | Percent of Participants Requiring High-Flow Nasal Cannula (HFNC) |
---|---|
Description | |
Time Frame | From randomization to Day 28 |
Outcome Measure Data
Analysis Population Description |
---|
ITT |
Arm/Group Title | Placebo | CSL312 |
---|---|---|
Arm/Group Description | CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously | Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously |
Measure Participants | 61 | 63 |
Number [percentage of participants] |
18.0
29.5%
|
14.3
22.7%
|
Title | Maximum Change From Baseline in Sequential Organ Failure Assessment (SOFA) Score |
---|---|
Description | The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems. Each system is scored from 0 (normal function) to 4 (most abnormal) with a total score ranging from 0 to 24. A high total SOFA score have been shown to be related to a worse outcome. |
Time Frame | From randomization to Day 28 |
Outcome Measure Data
Analysis Population Description |
---|
ITT. Participants with missing values were not included in the analysis. |
Arm/Group Title | Placebo | CSL312 |
---|---|---|
Arm/Group Description | CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously | Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously |
Measure Participants | 50 | 45 |
Mean (Standard Deviation) [score on a scale] |
0.5
(1.54)
|
0.1
(0.79)
|
Title | Change From Baseline in SOFA Total Score |
---|---|
Description | The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems. Each system is scored from 0 (normal function) to 4 (most abnormal) with a total score ranging from 0 to 24. A high total SOFA score have been shown to be related to a worse outcome. |
Time Frame | From randomization to Day 28 |
Outcome Measure Data
Analysis Population Description |
---|
ITT. Participants with missing values were not included in the analysis. |
Arm/Group Title | Placebo | CSL312 |
---|---|---|
Arm/Group Description | CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously | Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously |
Measure Participants | 15 | 12 |
Mean (Standard Deviation) [score on a scale] |
-1.0
(1.77)
|
-1.3
(0.89)
|
Title | Change From Baseline in the Individual Components of SOFA Score |
---|---|
Description | The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems. Each system is scored from 0 (normal function) to 4 (most abnormal) with a total score ranging from 0 to 24. A high total SOFA score have been shown to be related to a worse outcome. |
Time Frame | From randomization to Day 28 |
Outcome Measure Data
Analysis Population Description |
---|
ITT. Participants with missing values were not included in the analysis. |
Arm/Group Title | Placebo | CSL312 |
---|---|---|
Arm/Group Description | CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously | Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously |
Measure Participants | 61 | 63 |
Respiration Score |
-0.6
(1.32)
|
-1.2
(1.16)
|
Coagulation Score |
-0.1
(0.42)
|
0.4
(1.12)
|
Liver Score |
0.0
(0.22)
|
0.0
(0.00)
|
Cardiovascular Score |
0.4
(1.65)
|
0.5
(1.35)
|
Central Nervous System Score |
0.0
(0.00)
|
0.0
(0.19)
|
Renal Score |
0.3
(0.93)
|
0.5
(1.10)
|
Title | Length of Hospital Stay |
---|---|
Description | |
Time Frame | From randomization to Day 28 (+/- 2 days) |
Outcome Measure Data
Analysis Population Description |
---|
ITT |
Arm/Group Title | Placebo | CSL312 |
---|---|---|
Arm/Group Description | CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously | Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously |
Measure Participants | 61 | 63 |
Median (Full Range) [Days] |
7.00
|
6.50
|
Title | Number of Participants Experiencing Adverse Events (AEs) |
---|---|
Description | |
Time Frame | Up to 28 days after CSL312 or placebo administration |
Outcome Measure Data
Analysis Population Description |
---|
The Safety Analysis Set (SA) comprises all subjects in the ITT Analysis Set who receive any amount of CSL312 or placebo. |
Arm/Group Title | Placebo | CSL312 |
---|---|---|
Arm/Group Description | CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously | Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously |
Measure Participants | 59 | 58 |
Number [participants] |
40
65.6%
|
35
55.6%
|
Title | Percent of Participants Experiencing AEs |
---|---|
Description | |
Time Frame | Up to 28 days after CSL312 or placebo administration |
Outcome Measure Data
Analysis Population Description |
---|
SA |
Arm/Group Title | Placebo | CSL312 |
---|---|---|
Arm/Group Description | CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously | Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously |
Measure Participants | 59 | 58 |
Number [percentage of participants] |
67.8
111.1%
|
60.3
95.7%
|
Title | Number of Participants Experiencing Serious Adverse Events (SAEs) |
---|---|
Description | |
Time Frame | Up to 28 days after CSL312 or placebo administration |
Outcome Measure Data
Analysis Population Description |
---|
SA |
Arm/Group Title | Placebo | CSL312 |
---|---|---|
Arm/Group Description | CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously | Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously |
Measure Participants | 59 | 58 |
Number [participants] |
19
31.1%
|
20
31.7%
|
Title | Percent of Participants Experiencing SAEs |
---|---|
Description | |
Time Frame | Up to 28 days after CSL312 or placebo administration |
Outcome Measure Data
Analysis Population Description |
---|
SA |
Arm/Group Title | Placebo | CSL312 |
---|---|---|
Arm/Group Description | CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously | Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously |
Measure Participants | 59 | 58 |
Number [percentage of participants] |
32.2
52.8%
|
34.5
54.8%
|
Title | Number of Participants With Adverse Events of Special Interest (AESIs) |
---|---|
Description | |
Time Frame | Up to 28 days after CSL312 or placebo administration |
Outcome Measure Data
Analysis Population Description |
---|
SA |
Arm/Group Title | Placebo | CSL312 |
---|---|---|
Arm/Group Description | CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously | Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously |
Measure Participants | 59 | 58 |
Number [participants] |
6
9.8%
|
5
7.9%
|
Title | Percent of Participants With AESIs |
---|---|
Description | |
Time Frame | Up to 28 days after CSL312 or placebo administration |
Outcome Measure Data
Analysis Population Description |
---|
SA |
Arm/Group Title | Placebo | CSL312 |
---|---|---|
Arm/Group Description | CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously | Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously |
Measure Participants | 59 | 58 |
Number [percentage of participants] |
10.2
16.7%
|
8.6
13.7%
|
Title | Number of Participants With Anti-CSL312 Antibodies |
---|---|
Description | |
Time Frame | Up to 28 days after CSL312 or placebo administration |
Outcome Measure Data
Analysis Population Description |
---|
The pharmacodynamic (PD) Analysis Set will comprise all subjects in the Safety Analysis Set who received any amount of CSL312 or placebo and have ≥ 1 blood sample available for analysis of biomarkers. |
Arm/Group Title | Placebo | CSL312 |
---|---|---|
Arm/Group Description | CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously | Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously |
Measure Participants | 59 | 58 |
Number [participants] |
1
1.6%
|
0
0%
|
Title | Maximum Plasma Concentration (Cmax) of CSL312 |
---|---|
Description | |
Time Frame | Up to 28 days after CSL312 administration |
Outcome Measure Data
Analysis Population Description |
---|
The pharmacokinetic (PK) Analysis Set will comprise all subjects in the Safety Analysis Set who received any amount of CSL312 or placebo and have ≥ 1 blood sample available for CSL312 concentration measurement. |
Arm/Group Title | CSL312 |
---|---|
Arm/Group Description | Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously |
Measure Participants | 57 |
Mean (Standard Deviation) [ug/mL] |
147.335
(77.1286)
|
Title | Time to Maximum Plasma Concentration (Tmax) of CSL312 |
---|---|
Description | |
Time Frame | Up to 28 days after CSL312 administration |
Outcome Measure Data
Analysis Population Description |
---|
PK |
Arm/Group Title | CSL312 |
---|---|
Arm/Group Description | Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously |
Measure Participants | 57 |
Median (Full Range) [hours] |
0.667
|
Title | Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Measurable Concentration (AUC0-Last) of CSL312 |
---|---|
Description | |
Time Frame | Up to 28 days after CSL312 administration |
Outcome Measure Data
Analysis Population Description |
---|
PK |
Arm/Group Title | CSL312 |
---|---|
Arm/Group Description | Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously |
Measure Participants | 57 |
Mean (Standard Deviation) [h*ug/mL] |
15806.644
(9393.6295)
|
Title | Terminal Half-life (T1/2) of CSL312 |
---|---|
Description | |
Time Frame | Up to 28 days after CSL312 administration |
Outcome Measure Data
Analysis Population Description |
---|
PK. Participants with missing values were not included in the analysis. |
Arm/Group Title | CSL312 |
---|---|
Arm/Group Description | Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously |
Measure Participants | 9 |
Mean (Standard Deviation) [hours] |
226.165
(102.6690)
|
Adverse Events
Time Frame | Up to 28 days per participant after CSL312 or placebo administration | |||
---|---|---|---|---|
Adverse Event Reporting Description | All-Cause mortality uses ITT set and treatment emergent adverse events uses the safety analysis set. | |||
Arm/Group Title | Placebo | CSL312 | ||
Arm/Group Description | CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously | Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously | ||
All Cause Mortality |
||||
Placebo | CSL312 | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 11/61 (18%) | 11/63 (17.5%) | ||
Serious Adverse Events |
||||
Placebo | CSL312 | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 19/59 (32.2%) | 20/58 (34.5%) | ||
Blood and lymphatic system disorders | ||||
Anaemia | 1/59 (1.7%) | 1 | 0/58 (0%) | 0 |
Disseminated intravascular coagulation | 0/59 (0%) | 0 | 1/58 (1.7%) | 1 |
Thrombocytopenia | 1/59 (1.7%) | 1 | 0/58 (0%) | 0 |
Cardiac disorders | ||||
Cardiac arrest | 1/59 (1.7%) | 1 | 3/58 (5.2%) | 3 |
Sinus tachycardia | 0/59 (0%) | 0 | 1/58 (1.7%) | 1 |
Tachycardia | 0/59 (0%) | 0 | 1/58 (1.7%) | 1 |
General disorders | ||||
Asthenia | 1/59 (1.7%) | 1 | 0/58 (0%) | 0 |
Infections and infestations | ||||
Septic shock | 4/59 (6.8%) | 4 | 1/58 (1.7%) | 1 |
Pneumonia | 1/59 (1.7%) | 1 | 1/58 (1.7%) | 2 |
Sepsis | 2/59 (3.4%) | 2 | 0/58 (0%) | 0 |
Diverticulitis | 0/59 (0%) | 0 | 1/58 (1.7%) | 1 |
Enterobacter bacteraemia | 1/59 (1.7%) | 1 | 0/58 (0%) | 0 |
Enterobacter pneumonia | 1/59 (1.7%) | 1 | 0/58 (0%) | 0 |
Pneumonia escherichia | 1/59 (1.7%) | 1 | 0/58 (0%) | 0 |
Pneumonia streptococcal | 1/59 (1.7%) | 1 | 0/58 (0%) | 0 |
Injury, poisoning and procedural complications | ||||
Subdural haematoma | 1/59 (1.7%) | 1 | 0/58 (0%) | 0 |
Metabolism and nutrition disorders | ||||
Hypoglycaemia | 1/59 (1.7%) | 1 | 0/58 (0%) | 0 |
Nervous system disorders | ||||
Brain hypoxia | 0/59 (0%) | 0 | 1/58 (1.7%) | 1 |
Cerebellar infarction | 1/59 (1.7%) | 1 | 0/58 (0%) | 0 |
Cerebral infarction | 1/59 (1.7%) | 1 | 0/58 (0%) | 0 |
Haemorrhagic stroke | 1/59 (1.7%) | 1 | 0/58 (0%) | 0 |
Subarachnoid haemorrhage | 1/59 (1.7%) | 1 | 0/58 (0%) | 0 |
Psychiatric disorders | ||||
Mental status changes | 0/59 (0%) | 0 | 1/58 (1.7%) | 1 |
Renal and urinary disorders | ||||
Acute kidney injury | 2/59 (3.4%) | 2 | 1/58 (1.7%) | 1 |
Respiratory, thoracic and mediastinal disorders | ||||
Respiratory failure | 7/59 (11.9%) | 8 | 6/58 (10.3%) | 6 |
Hypoxia | 1/59 (1.7%) | 1 | 4/58 (6.9%) | 5 |
Acute respiratory failure | 1/59 (1.7%) | 1 | 4/58 (6.9%) | 4 |
Pulmonary embolism | 2/59 (3.4%) | 2 | 2/58 (3.4%) | 3 |
Pneumothorax | 1/59 (1.7%) | 1 | 1/58 (1.7%) | 1 |
Acute respiratory distress syndrome | 1/59 (1.7%) | 1 | 0/58 (0%) | 0 |
Dyspnoea | 1/59 (1.7%) | 1 | 0/58 (0%) | 0 |
Epistaxis | 0/59 (0%) | 0 | 1/58 (1.7%) | 1 |
Vascular disorders | ||||
Deep vein thrombosis | 1/59 (1.7%) | 1 | 3/58 (5.2%) | 3 |
Hypotension | 3/59 (5.1%) | 3 | 1/58 (1.7%) | 1 |
Arterial thrombosis | 1/59 (1.7%) | 1 | 0/58 (0%) | 0 |
Peripheral artery thrombosis | 1/59 (1.7%) | 1 | 0/58 (0%) | 0 |
Peripheral ischaemia | 0/59 (0%) | 0 | 1/58 (1.7%) | 1 |
Venous thrombosis | 1/59 (1.7%) | 1 | 0/58 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
Placebo | CSL312 | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 21/59 (35.6%) | 18/58 (31%) | ||
Cardiac disorders | ||||
Atrial fibrillation | 5/59 (8.5%) | 5 | 2/58 (3.4%) | 2 |
Bradycardia | 0/59 (0%) | 0 | 3/58 (5.2%) | 3 |
Gastrointestinal disorders | ||||
Constipation | 3/59 (5.1%) | 3 | 0/58 (0%) | 0 |
Infections and infestations | ||||
Septic shock | 2/59 (3.4%) | 2 | 3/58 (5.2%) | 3 |
Investigations | ||||
Transaminases increased | 4/59 (6.8%) | 4 | 1/58 (1.7%) | 1 |
Fibrin D dimer increased | 3/59 (5.1%) | 3 | 1/58 (1.7%) | 1 |
Metabolism and nutrition disorders | ||||
Hyperglycaemia | 5/59 (8.5%) | 5 | 5/58 (8.6%) | 5 |
Hyperkalaemia | 3/59 (5.1%) | 3 | 2/58 (3.4%) | 2 |
Hypokalaemia | 3/59 (5.1%) | 3 | 2/58 (3.4%) | 2 |
Psychiatric disorders | ||||
Anxiety | 2/59 (3.4%) | 2 | 3/58 (5.2%) | 3 |
Renal and urinary disorders | ||||
Acute kidney injury | 6/59 (10.2%) | 6 | 0/58 (0%) | 0 |
Respiratory, thoracic and mediastinal disorders | ||||
Dyspnoea | 3/59 (5.1%) | 3 | 2/58 (3.4%) | 2 |
Vascular disorders | ||||
Hypotension | 6/59 (10.2%) | 6 | 2/58 (3.4%) | 2 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
Results Point of Contact
Name/Title | Study Director |
---|---|
Organization | CSL Behring |
Phone | 610-878-4000 |
clinicaltrials@cslbehring.com |
- CSL312_COVID-19