Canakinumab in Covid-19 Cardiac Injury (The Three C Study)
Condition: COVID-19; SARS-CoV 2
MeSH terms: COVID-19
Intervention: Canakinumab Injection 600mg; Canakinumab Injection 300mg; Placebos
Intervention description: Subjects will be given one-time intravenous infusion of 600 mg of canakinumab (8 mg/kg for patients </= 40 kg) in 250 mL of 5% dextrose infused IV over 2 hours; Subjects will be given one-time intravenous infusion of 300 mg of canakinumab (4 mg/kg for patients </= 40 kg) in 250 mL of 5% dextrose infused IV over 2 hours; 250 mL of 5% dextrose infused IV over 2 hours
Intervention MeSH terms: 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: 45.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      TThe purpose of this prospective, Phase 2, single center, blinded, randomized controlled
      study is to demonstrate as a proof of concept that early treatment with canakinumab prevents
      progressive heart and respiratory failure in patients with COVID-19 infection. These results
      will lead to and inform a Phase III randomized placebo-controlled trial.
    

Eligibility criteria:

        Inclusion Criteria: Subjects eligible for inclusion in this study must meet all of the
        following criteria:

          1. Written informed consent must be obtained before any assessment is performed

          2. Hospitalized due to COVID-19 infection

          3. Documented SARS-CoV2 acute myocardial injury: Defined as upper respiratory tract
             specimen positive for COVID-19 AND Troponin T greater than 99th percentile upper
             reference range without signs or symptoms of acute myocardial ischemia

          4. NT-proBNP greater than the age-adjusted upper reference limit

          5. Receiving current standard therapy

          6. C-reactive protein (CRP) > 50 mg/L

        Exclusion Criteria: Subjects meeting any of the following criteria are not eligible for
        inclusion in this study.

          1. Alternative explanation for acute cardiac injury (Type I or Type II MI according to
             4th Universal Definition of Myocardial Infarction, which in addition to a rise and
             fall of troponin above the 99th percentile upper reference limit, includes symptoms of
             acute myocardial ischemia, new ischemic ECG changes, development of pathologic Q
             waves, and imaging evidence of damage in a pattern consistent with an ischemic
             etiology)

          2. Chronic Systolic Heart Failure with EF<35%

          3. Age < 18 years-old

          4. Uncontrolled systemic bacterial or fungal infection

          5. Concomitant viral infection (e.g., Influenza or other respiratory virus)

          6. Pregnant. Breast-feeding women are eligible with the decision to continue or
             discontinue breast-feeding during therapy taking into account the risk of infant
             exposure, the benefits of breast-feeding to the infant, and benefits of treatment to
             the mother.

          7. On mechanical circulatory support

          8. On mechanical ventilation for greater than 48 hours

          9. Resuscitated cardiac arrest

         10. Has a known hypersensitivity to canakinumab or any of its excipients

         11. Neutrophil count <1000/mm3

         12. Has a history of myeloproliferative disorder or active malignancy receiving
             chemotherapy

         13. Known active tuberculosis or history of incompletely treated tuberculosis

         14. Current treatment with immunosuppressive agents

         15. Chronic prednisone use >10 mg/daily (for more than 3 weeks prior to admission)

         16. Has a history of solid-organ or bone marrow transplant

         17. Severe pre-existing liver disease with clinically significant portal hypertension

         18. End-stage renal disease on chronic renal replacement therapy

         19. Enrollment in another investigational study using immunosuppressive therapy

         20. In the opinion of the investigator and clinical team, should not participate in the
             study

         21. If male and sexually active, must have documented vasectomy or must practice birth
             control and not donate sperm during the study and for 3 months after study drug
             administration.

         22. Women of child-bearing potential, defined as all women physiologically capable of
             becoming pregnant, unless they are using highly effective methods of contraception
             during dosing of investigational drug. Such methods include:

               -  Total abstinence (when this is in line with the preferred and usual lifestyle of
                  the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal,
                  post-ovulation methods) and withdrawal are not acceptable methods of
                  contraception

               -  Female sterilization (have had surgical bilateral oophorectomy with or without
                  hysterectomy), total hysterectomy, or bilateral tubal ligation at least six weeks
                  before taking study treatment. In case of oophorectomy alone, only when the
                  reproductive status of the woman has been confirmed by follow up hormone level
                  assessment

               -  Male sterilization (at least 6 months prior to screening). For female subjects on
                  the study, the vasectomized male partner should be the sole partner for that
                  subject

               -  Use of oral, (estrogen and progesterone), injected or implanted hormonal methods
                  of contraception or placement of an intrauterine device (IUD) or intrauterine
                  system (IUS), or other forms of hormonal contraception that have comparable
                  efficacy (failure rate <1%), for example hormone vaginal ring or transdermal
                  hormone contraception