Canakinumab in Covid-19 Cardiac Injury (The Three C Study)

NCT ID: NCT04365153

Last Updated: 2021-04-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-04-24
• Study Completion Date: 2021-04-01

Brief 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.

Detailed Description

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

The study will be performed in approximately 7 months total, starting from the first patient enrolled with enrollment expected to complete within 2 months. The follow-up period is 5 months for each patient enrolled. The end of the study, including statistical analysis and drafting of the final report is expected within 1 month from the last patient enrolled.

A total of 45 patients will be randomized using a 1:1:1 allocation ratio: 15 subjects will receive 600 mg intravenous canakinumab (8 mg/kg if </= 40 kg), 15 subjects will receive 300 mg intravenous canakinumab (4 mg/kg if </= 40 kg), and 15 patients will receive placebo infusion.

The investigator, clinical team, and subject will be blinded to treatment assignment.

Conditions

COVID-19; SARS-CoV 2

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

High Dose Intervention

600 mg of canakinumab (8 mg/kg for patients \</= 40 kg)

Group Type: ACTIVE_COMPARATOR

Canakinumab Injection 600mg

Intervention Type: DRUG

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

Low Dose Intervention

300 mg of canakinumab (4 mg/kg for patients \</= 40 kg)

Group Type: ACTIVE_COMPARATOR

Canakinumab Injection 300mg

Intervention Type: DRUG

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

Control

Placebo

Group Type: PLACEBO_COMPARATOR

Placebos

Intervention Type: DRUG

250 mL of 5% dextrose infused IV over 2 hours

Interventions

Canakinumab Injection 600mg

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

Intervention Type: DRUG

Canakinumab Injection 300mg

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

Intervention Type: DRUG

Placebos

250 mL of 5% dextrose infused IV over 2 hours

Intervention Type: DRUG

Other Intervention Names

ACZ885; ACZ885; Control

Eligibility Criteria

Inclusion 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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis

INDUSTRY

Sponsor Role: collaborator

The Cleveland Clinic

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Paul C Cremer, M. D.

Role: PRINCIPAL_INVESTIGATOR

The Cleveland Clinic

Locations

Cleveland Clinic Florida

Weston, Florida, United States

Cleveland Clinic

Cleveland, Ohio, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

IND 149328

Identifier Type: -

Identifier Source: org_study_id