Treatment With CSL312 in Adults With Coronavirus Disease 2019 (COVID-19)
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT04409509 |
Recruitment Status :
Completed
First Posted : June 1, 2020
Results First Posted : January 24, 2022
Last Update Posted : January 24, 2022
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Condition or disease | Intervention/treatment | Phase |
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Coronavirus Disease 2019 (COVID-19) | Biological: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody Drug: Placebo | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 124 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
Primary Purpose: | Treatment |
Official Title: | A Phase 2, Multicenter, Double Blind, Randomized, Placebo-Controlled Study to Evaluate CSL312 in Coronavirus Disease 2019 (COVID 19) |
Actual Study Start Date : | July 1, 2020 |
Actual Primary Completion Date : | January 12, 2021 |
Actual Study Completion Date : | January 12, 2021 |

Arm | Intervention/treatment |
---|---|
Experimental: CSL312
Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously
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Biological: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody
Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously |
Placebo Comparator: Placebo
CSL312 diluent administered intravenously
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Drug: Placebo
CSL312 diluent administered intravenously |
- The Percent of Participants With Tracheal Intubation or Death Prior to Tracheal Intubation [ Time Frame: From randomization to Day 28 ]
- Percent of Participants With Death From All Causes [ Time Frame: From randomization to Day 28 ]
- Percent of Participants With Tracheal Intubation [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: From randomization to Day 28 ]
- Percent of Participants Requiring Extracorporeal Membrane Oxygenation (ECMO) [ Time Frame: 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) [ Time Frame: From randomization to Day 28 ]
- Maximum Change From Baseline in Sequential Organ Failure Assessment (SOFA) Score [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: From randomization to Day 28 (+/- 2 days) ]
- Number of Participants Experiencing Adverse Events (AEs) [ Time Frame: Up to 28 days after CSL312 or placebo administration ]
- Percent of Participants Experiencing AEs [ Time Frame: Up to 28 days after CSL312 or placebo administration ]
- Number of Participants Experiencing Serious Adverse Events (SAEs) [ Time Frame: Up to 28 days after CSL312 or placebo administration ]
- Percent of Participants Experiencing SAEs [ Time Frame: Up to 28 days after CSL312 or placebo administration ]
- Number of Participants With Adverse Events of Special Interest (AESIs) [ Time Frame: Up to 28 days after CSL312 or placebo administration ]
- Percent of Participants With AESIs [ Time Frame: Up to 28 days after CSL312 or placebo administration ]
- Number of Participants With Anti-CSL312 Antibodies [ Time Frame: Up to 28 days after CSL312 or placebo administration ]
- Maximum Plasma Concentration (Cmax) of CSL312 [ Time Frame: Up to 28 days after CSL312 administration ]
- Time to Maximum Plasma Concentration (Tmax) of CSL312 [ Time Frame: 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 [ Time Frame: Up to 28 days after CSL312 administration ]
- Terminal Half-life (T1/2) of CSL312 [ Time Frame: Up to 28 days after CSL312 administration ]

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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
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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
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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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04409509
United States, Florida | |
Nova Clinical Research, LLC | |
Bradenton, Florida, United States, 34209 | |
Theia Clinical Research, LLC | |
Saint Petersburg, Florida, United States, 33707 | |
United States, Iowa | |
MercyOne North Iowa Medical Center | |
Mason City, Iowa, United States, 50401 | |
Northeast Iowa Medical Education Foundation | |
Waterloo, Iowa, United States, 50702 | |
United States, Massachusetts | |
Lahey Hospital and Medical Center | |
Burlington, Massachusetts, United States, 01805 | |
United States, Mississippi | |
University of Mississippi Medical Center | |
Jackson, Mississippi, United States, 39216 | |
United States, New Jersey | |
Holy Name Hospital | |
Teaneck, New Jersey, United States, 07666 | |
Inspira Health Center Vineland | |
Vineland, New Jersey, United States, 08360 | |
United States, New York | |
Sisters of Charity Hospital/ St. Joseph's Campus | |
Buffalo, New York, United States, 14225 | |
United States, North Carolina | |
Carolina Institute for Clinical Research | |
Fayetteville, North Carolina, United States, 28304 | |
United States, South Dakota | |
Monument Health Clinical Research | |
Rapid City, South Dakota, United States, 57701 | |
United States, Texas | |
PharmaTex Research | |
Amarillo, Texas, United States, 79109 | |
UT Health Science Center, McGovern Medical School | |
Houston, Texas, United States, 77030 | |
United States, Virginia | |
Inova Alexandria Hospital | |
Alexandria, Virginia, United States, 22304 |
Study Director: | Study Director | CSL Behring |
Documents provided by CSL Behring:
Responsible Party: | CSL Behring |
ClinicalTrials.gov Identifier: | NCT04409509 |
Other Study ID Numbers: |
CSL312_COVID-19 |
First Posted: | June 1, 2020 Key Record Dates |
Results First Posted: | January 24, 2022 |
Last Update Posted: | January 24, 2022 |
Last Verified: | January 2022 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Yes |
Plan Description: | CSL will consider requests to share Individual Patient Data (IPD) from systematic review groups or bona-fide researchers. For information on the process and requirements for submitting a voluntary data sharing request for IPD, please contact CSL at clinicaltrials@cslbehring.com. Applicable country specific privacy and other laws and regulations will be considered and may prevent sharing of IPD. If the request is approved and the researcher has executed an appropriate data sharing agreement, IPD that has been appropriately anonymized will be available. |
Supporting Materials: |
Study Protocol Statistical Analysis Plan (SAP) |
Time Frame: | IPD requests may be submitted to CSL no earlier than 12 months after publication of the results of this study via an article made available on a public website. |
Access Criteria: | Requests may only be made by systematic review groups or bona-fide researchers whose proposed use of the IPD is non-commercial in nature and has been approved by an internal review committee. An IPD request will not be considered by CSL unless the proposed research question seeks to answer a significant and unknown medical science or patient care question as determined by CSL's internal review committee. The requesting party must execute an appropriate data sharing agreement before IPD will be made available. |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Prevention of respiratory failure |
COVID-19 Coronavirus Infections Respiratory Tract Infections Infections Pneumonia, Viral Pneumonia Virus Diseases Coronaviridae Infections |
Nidovirales Infections RNA Virus Infections Lung Diseases Respiratory Tract Diseases Antibodies Antibodies, Monoclonal Immunologic Factors Physiological Effects of Drugs |