Treatment With CSL312 in Adults With Coronavirus Disease 2019 (COVID-19)
Condition: Coronavirus Disease 2019 (COVID-19)
MeSH terms: COVID-19; Coronavirus Infections
Intervention: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody; Placebo
Intervention description: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously; CSL312 diluent administered intravenously
Intervention MeSH terms: Antibodies; Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 124.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Prevention of respiratory failure

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)
    

Eligibility 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