Treatment With CSL312 in Adults With Coronavirus Disease 2019 (COVID-19)
- Conditions
- Coronavirus Disease 2019 (COVID-19)
- Interventions
- Biological: Garadacimab, Factor XIIa Antagonist Monoclonal AntibodyDrug: Placebo
- Registration Number
- NCT04409509
- Lead Sponsor
- CSL Behring
- 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)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 124
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Age ≥ 18 years
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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.
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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%
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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.
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Pregnant or breastfeeding (female subjects)
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Intubated and require mechanical ventilation (including ECMO) at the time of randomization
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In the opinion of the investigator, the subject is expected to be intubated in the first 24 hours after IMP administration
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Has a Do-Not-Intubate (DNI) or Do-Not-Resuscitate (DNR) order
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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
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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)
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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)
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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
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Currently receiving a therapy not permitted during the study.
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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
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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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description CSL312 Garadacimab, Factor XIIa Antagonist Monoclonal Antibody Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Placebo Placebo CSL312 diluent administered intravenously
- Primary Outcome Measures
Name Time Method The Percent of Participants With Tracheal Intubation or Death Prior to Tracheal Intubation From randomization to Day 28
- Secondary Outcome Measures
Name Time Method 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 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.
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 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) 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 Maximum Plasma Concentration (Cmax) of CSL312 Up to 28 days after CSL312 administration Terminal Half-life (T1/2) of CSL312 Up to 28 days after CSL312 administration 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 High-Flow Nasal Cannula (HFNC) From randomization to Day 28 Number of Participants With Anti-CSL312 Antibodies Up to 28 days after CSL312 or placebo administration 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.
Number of Participants With Adverse Events of Special Interest (AESIs) Up to 28 days after CSL312 or placebo 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 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.
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.
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.
Number of Participants Experiencing Adverse Events (AEs) Up to 28 days after CSL312 or placebo administration Percent of Participants Experiencing SAEs Up to 28 days after CSL312 or placebo administration Percent of Participants With AESIs Up to 28 days after CSL312 or placebo administration
Trial Locations
- Locations (14)
Lahey Hospital and Medical Center
🇺🇸Burlington, Massachusetts, United States
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
Holy Name Hospital
🇺🇸Teaneck, New Jersey, United States
Inspira Health Center Vineland
🇺🇸Vineland, New Jersey, United States
UT Health Science Center, McGovern Medical School
🇺🇸Houston, Texas, United States
Sisters of Charity Hospital/ St. Joseph's Campus
🇺🇸Buffalo, New York, United States
Theia Clinical Research, LLC
🇺🇸Saint Petersburg, Florida, United States
MercyOne North Iowa Medical Center
🇺🇸Mason City, Iowa, United States
Nova Clinical Research, LLC
🇺🇸Bradenton, Florida, United States
Northeast Iowa Medical Education Foundation
🇺🇸Waterloo, Iowa, United States
PharmaTex Research
🇺🇸Amarillo, Texas, United States
Carolina Institute for Clinical Research
🇺🇸Fayetteville, North Carolina, United States
Monument Health Clinical Research
🇺🇸Rapid City, South Dakota, United States
Inova Alexandria Hospital
🇺🇸Alexandria, Virginia, United States