NCT04409509CompletedPhase 2
A Phase 2, Multicenter, Double Blind, Randomized, Placebo-Controlled Study to Evaluate CSL312 in Coronavirus Disease 2019 (COVID 19)
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- CSL Behring
- Enrollment
- 124
- Locations
- 14
- Primary Endpoint
- The Percent of Participants With Tracheal Intubation or Death Prior to Tracheal Intubation
Study Overview
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)
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- 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
- •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
Arms & Interventions
CSL312
Experimental
Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously
Intervention: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody (Biological)
Placebo
Placebo Comparator
CSL312 diluent administered intravenously
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
The Percent of Participants With Tracheal Intubation or Death Prior to Tracheal Intubation
Time Frame: From randomization to Day 28
Secondary Outcomes
- 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)
- Maximum Change From Baseline in Sequential Organ Failure Assessment (SOFA) Score(From randomization to Day 28)
- Change From Baseline in the Individual Components of SOFA Score(From randomization to Day 28)
- 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)
- Number of Participants With Adverse Events of Special Interest (AESIs)(Up to 28 days after CSL312 or placebo administration)
- Percent of Participants Within Each of the Categories of the NIAID at End of Study(Day 28)
- 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)
- 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)
- 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)
- Change From Baseline in SOFA Total Score(From randomization to Day 28)
- 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)
Investigators
Study Sites (14)
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