Canakinumab for Cardiovascular Disease

(TECTONIC Trial)

Overseen By Michael C Honigberg, MD, MPP

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Massachusetts General Hospital

Must not be taking: Steroids, Anti-inflammatories

Disqualifiers: Blood malignancy, Organ transplant, others

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

Duration: 48 weeks

120 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as prescription steroids or anti-inflammatory drugs, if you are currently using them. If you have used oral steroids or prescription anti-inflammatory medications for more than 7 days in the past month, or IV/IM steroids in the past 3 months, you may not be eligible to participate.

How is the drug canakinumab different from other treatments for cardiovascular disease?

Canakinumab is unique because it is a monoclonal antibody that targets interleukin-1β, a protein involved in inflammation, which is not a common approach for treating cardiovascular disease. It is administered as a subcutaneous injection every 8 weeks, offering a novel anti-inflammatory strategy compared to traditional cardiovascular treatments. ^{1 2 3 4 5}

What is the purpose of this trial?

The primary goal of this clinical trial is to test the hypothesis that the drug canakinumab (anti-IL-1B monoclonal antibody) decreases vascular inflammation when used by people with a history of coronary artery disease, including those with and without clonal hematopoiesis driven by mutations in TET2.

Eligibility Criteria

This trial is for individuals with a history of coronary artery disease. It's specifically looking at those who may also have clonal hematopoiesis, which can be driven by mutations in the TET2 gene.

Inclusion Criteria

My genetic test shows I have TET2 CHIP or no CHIP mutations.

I had a heart attack or got a coronary stent over 6 months ago.

Exclusion Criteria

I use PDE5 inhibitors and won't stop taking them before my CCTA scan.

My liver is healthy and my liver tests are within normal limits.

I do not have conditions like severe eye pressure or heart valve issues.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Baseline assessment includes coronary CT angiography and SPECT imaging for a subset of participants

1 week

1 visit (in-person)

Treatment

Participants receive canakinumab or placebo injections every 3 months for 4 doses

48 weeks

4 visits (in-person)

Imaging Assessment

Repeat imaging assessments for vascular inflammation

1 week

1 visit (in-person)

Final Study and Safety Assessments

Participants undergo final study and safety assessments

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Canakinumab

Trial Overview The study tests if canakinumab, an anti-inflammatory drug targeting IL-1 beta, reduces vascular inflammation compared to a saline placebo in participants with coronary artery disease.

Participant Groups

Group I: Treatment: Canakinumab Experimental Treatment 1 Intervention

Participants with and without TET2 CHIP will receive 150mg of canakinumab every 3 months for 4 doses as part of the randomized clinical trial part of this proposal.

Group II: Placebo: Control Placebo Group 1 Intervention

Participants with and without TET2 CHIP will receive placebo injection every 3 months for 4 doses as part of the randomized clinical trial part of this proposal.

Canakinumab is already approved in European Union, United States for the following indications:

Approved in European Union as Ilaris for:

• Cryopyrin-Associated Periodic Syndromes (CAPS)
• Familial Cold Autoinflammatory Syndrome (FCAS)
• Muckle-Wells Syndrome (MWS)
• Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS)
• Hyperimmunoglobulin D Syndrome (HIDS)/Mevalonate Kinase Deficiency (MKD)
• Familial Mediterranean Fever (FMF)
• Systemic Juvenile Idiopathic Arthritis (SJIA)
• Adult-Onset Still's Disease (AOSD)

Approved in United States as Ilaris for:

• Cryopyrin-Associated Periodic Syndromes (CAPS)
• Familial Cold Autoinflammatory Syndrome (FCAS)
• Muckle-Wells Syndrome (MWS)
• Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS)
• Hyperimmunoglobulin D Syndrome (HIDS)/Mevalonate Kinase Deficiency (MKD)
• Familial Mediterranean Fever (FMF)
• Systemic Juvenile Idiopathic Arthritis (SJIA)
• Adult-Onset Still's Disease (AOSD)

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Broad Institute

Collaborator

Trials

21

Recruited

16,300+

Yale University

Collaborator

Trials

1,963

Recruited

3,046,000+

Broad Institute of MIT and Harvard

Collaborator

Trials

21

Recruited

16,300+

Findings from Research

Canakinumab is an effective treatment for inflammatory diseases like familial cold auto-inflammatory syndrome and Muckle-Wells syndrome, as it neutralizes IL-1beta signaling to reduce inflammation.

The drug is generally well-tolerated with no serious adverse effects reported, and it offers benefits such as bimonthly administration and approval for use in children, making it a promising option for various autoimmune conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Canakinumab. Dhimolea, E.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

A case report of locally invasive Aspergillus fumigatus infection in a patient on canakinumab. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Canakinumab. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Pharmacokinetic and pharmacodynamic properties of canakinumab, a human anti-interleukin-1β monoclonal antibody. [2021]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Canakinumab: in patients with cryopyrin-associated periodic syndromes. [2019]

5. Netherlands pubmed.ncbi.nlm.nih.gov

The cost-effectiveness of canakinumab for secondary prevention of cardiovascular disease: The Australian healthcare perspective. [2020]