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

NCT04365153 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: IND 149328
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 2

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.

Conditions

COVID-19; SARS-CoV 2

Outcome Measures

Primary Outcomes (1)

• 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

  Up to day 14

Secondary Outcomes (1)

• All-cause Mortality

  Up to day 28

Study Arms (3)

High Dose Intervention

ACTIVE COMPARATOR

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

Drug: Canakinumab Injection 600mg

Low Dose Intervention

ACTIVE COMPARATOR

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

Drug: Canakinumab Injection 300mg

Control

PLACEBO COMPARATOR

Placebo

Drug: Placebos

Interventions

Canakinumab Injection 600mg 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

Also known as: ACZ885

High Dose Intervention

Canakinumab Injection 300mg 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

Also known as: ACZ885

Low Dose Intervention

Placebos DRUG

250 mL of 5% dextrose infused IV over 2 hours

Also known as: Control

Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• The Cleveland Clinic: lead
• Novartis: collaborator

Study Sites (2)

Cleveland Clinic Florida

Weston, Florida, 33331, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Conditions

COVID-19

Interventions

canakinumab

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Paul C. Cremer, MD
• Organization: Cleveland Clinic

cremerp@ccf.org

216-444-6765

Study Officials

• Paul C Cremer, M. D.

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 24, 2020
• First Posted: April 28, 2020
• Study Start: April 24, 2020
• Primary Completion: February 2, 2021
• Study Completion: April 1, 2021
• Last Updated: April 15, 2021
• Results First Posted: April 15, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)