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

Primary Purpose

COVID-19, SARS-CoV 2

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Canakinumab Injection 600mg
Canakinumab Injection 300mg
Placebos
Sponsored by
The Cleveland Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for COVID-19

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Cleveland Clinic Florida
  • Cleveland Clinic

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Active Comparator

Placebo Comparator

Arm Label

High Dose Intervention

Low Dose Intervention

Control

Arm Description

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

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

Placebo

Outcomes

Primary Outcome Measures

Number of Participants With Clinical Improvement at Day 14
Number of patients with either an improvement of two points on a seven category ordinal scale or discharge from the hospital

Secondary Outcome Measures

All-cause Mortality
Number of patients who expired after treatment

Full Information

First Posted
April 24, 2020
Last Updated
April 13, 2021
Sponsor
The Cleveland Clinic
Collaborators
Novartis
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1. Study Identification

Unique Protocol Identification Number
NCT04365153
Brief Title
Canakinumab in Covid-19 Cardiac Injury (The Three C Study)
Official Title
Canakinumab to Reduce Deterioration of Cardiac and Respiratory Function in SARSCoV2 Associated Acute Myocardial Injury With Heightened Inflammation
Study Type
Interventional

2. Study Status

Record Verification Date
April 2021
Overall Recruitment Status
Completed
Study Start Date
April 24, 2020 (Actual)
Primary Completion Date
February 2, 2021 (Actual)
Study Completion Date
April 1, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The Cleveland Clinic
Collaborators
Novartis

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19, SARS-CoV 2

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
45 (Actual)

8. Arms, Groups, and Interventions

Arm Title
High Dose Intervention
Arm Type
Active Comparator
Arm Description
600 mg of canakinumab (8 mg/kg for patients </= 40 kg)
Arm Title
Low Dose Intervention
Arm Type
Active Comparator
Arm Description
300 mg of canakinumab (4 mg/kg for patients </= 40 kg)
Arm Title
Control
Arm Type
Placebo Comparator
Arm Description
Placebo
Intervention Type
Drug
Intervention Name(s)
Canakinumab Injection 600mg
Other Intervention Name(s)
ACZ885
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
Intervention Type
Drug
Intervention Name(s)
Canakinumab Injection 300mg
Other Intervention Name(s)
ACZ885
Intervention Description
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
Intervention Name(s)
Placebos
Other Intervention Name(s)
Control
Intervention Description
250 mL of 5% dextrose infused IV over 2 hours
Primary Outcome Measure Information:
Title
Number of Participants With Clinical Improvement at Day 14
Description
Number of patients with either an improvement of two points on a seven category ordinal scale or discharge from the hospital
Time Frame
Up to day 14
Secondary Outcome Measure Information:
Title
All-cause Mortality
Description
Number of patients who expired after treatment
Time Frame
Up to day 28

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subjects eligible for inclusion in this study must meet all of the following criteria: Written informed consent must be obtained before any assessment is performed Hospitalized due to COVID-19 infection 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 NT-proBNP greater than the age-adjusted upper reference limit Receiving current standard therapy C-reactive protein (CRP) > 50 mg/L Exclusion Criteria: Subjects meeting any of the following criteria are not eligible for inclusion in this study. 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) Chronic Systolic Heart Failure with EF<35% Age < 18 years-old Uncontrolled systemic bacterial or fungal infection Concomitant viral infection (e.g., Influenza or other respiratory virus) 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. On mechanical circulatory support On mechanical ventilation for greater than 48 hours Resuscitated cardiac arrest Has a known hypersensitivity to canakinumab or any of its excipients Neutrophil count <1000/mm3 Has a history of myeloproliferative disorder or active malignancy receiving chemotherapy Known active tuberculosis or history of incompletely treated tuberculosis Current treatment with immunosuppressive agents Chronic prednisone use >10 mg/daily (for more than 3 weeks prior to admission) Has a history of solid-organ or bone marrow transplant Severe pre-existing liver disease with clinically significant portal hypertension End-stage renal disease on chronic renal replacement therapy Enrollment in another investigational study using immunosuppressive therapy In the opinion of the investigator and clinical team, should not participate in the study 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. 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paul C Cremer, M. D.
Organizational Affiliation
The Cleveland Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cleveland Clinic Florida
City
Weston
State/Province
Florida
ZIP/Postal Code
33331
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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