Effects of IL-1 Beta Inhibition on Vascular Inflammation in TET2 Clonal Hematopoiesis

NCT06691217 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 2024P002825
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

ASCVD Management; Vascular Inflammation; ASCVD

Keywords

CHIP; TET2 CHIP; Clonal Hematopoiesis; Vascular Inflammation; ASCVD; ASCVD management

Outcome Measures

Primary Outcomes (1)

• Between-group difference (canakinumab versus placebo) in the change in perivascular fat attenuation index (Hounsfield units) measured by coronary computed tomography angiography

  48 weeks

Secondary Outcomes (1)

• Between-group difference (canakinumab versus placebo) in the percent change in TET2 variant allele fraction (proportion of mutated alleles in peripheral blood cells) ascertained by targeted genomic sequencing

  48 weeks

Other Outcomes (16)

• Between-group difference (canakinumab vs. placebo) in the change in the fatty attenuation index in the vessel with the highest fatty attenuation index (measured by coronary computed tomography angiography) in each participant

  48 weeks

• Between-group difference (canakinumab versus placebo) in the fatty attenuation index (FAI) Score in all 3 major coronary arteries

  48 weeks

• Between-group differences in effect of canakinumab on perivascular fatty attenuation index (measured using coronary computed tomography angiography) between those with TET2 CHIP vs. no CHIP using pooled placebo groups

  48 weeks

Study Arms (2)

Placebo: Control

PLACEBO COMPARATOR

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.

Drug: Saline (NaCl 0,9 %) (placebo)

Treatment: Canakinumab

EXPERIMENTAL

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.

Drug: CANAKINUMAB (ILARIS®)

Interventions

CANAKINUMAB (ILARIS®) DRUG

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.

Treatment: Canakinumab

Saline (NaCl 0,9 %) (placebo) DRUG

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.

Placebo: Control

Eligibility Criteria

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

You may qualify if:

• years or older
• Prior heart attack or coronary stent procedure \>180 days before baseline imaging
• Presence of either TET2 CHIP or no CHIP variants on prior sequencing

You may not qualify if:

• placement of a drug-eluting stent in a proximal coronary arterial segment \<180 days before baseline imaging
• prior coronary artery bypass grafting
• pregnancy or breastfeeding
• history of blood malignancy or current solid-tumor malignancy
• history of organ or stem cell transplantation
• current treatment with prescription, systemic (oral, IV \[intravenous\], or IM \[intramuscular\]) steroids or anti-inflammatory/immune suppressant medical therapies (including colchicine but excluding topical therapies, UV therapy, ASA-derivative therapies, or NSAIDS) for autoimmune/inflammatory diseases, post-transplant care, asthma, or pain
• use of oral steroids or prescription oral anti-inflammatory/immune suppressant medication for \>7 days within the past 1 month
• use of IV or IM steroids or IV or IM anti-inflammatory/immune suppressant medication within the past 3 months
• known allergy to dextran's and/or DTPA and/or radiometals and/or severe allergy to iodinated contrast media
• estimated glomerular filtration rate (eGFR) \< 45 ml/min/1.73 m2
• contraindications to nitroglycerin known narrow angle glaucoma, or known severe aortic stenosis
• use of phosphodiesterase type 5 inhibitor AND refusal to abstain from use of these medications within the 5 days prior to scheduled CCTA scan
• significant radiation exposure (40msV) received within the past 12 months
• concurrent enrollment in another research study judged by the investigators to interfere with the current study
• known active or recurrent hepatic disease (including cirrhosis or ALT/AST levels \>3 times the upper limit oof or total bilirubin \>2 times the upper limits of normal)

Sponsors & Collaborators

• National Institutes of Health (NIH): collaborator
• Broad Institute of MIT and Harvard: collaborator
• Massachusetts General Hospital: lead
• Yale University: collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

MeSH Terms

Interventions

canakinumab; Sodium Chloride

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Central Study Contacts

Michael C Honigberg, MD MPP

CONTACT

617-726-1843; mhonigberg@mgh.harvard.edu

Mabel Toribio, MD

CONTACT

(617)-724-2826; mptoribio@mgh.harvard.edu

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: PRINCIPAL INVESTIGATOR
• PI Title: MD, MPP

Model Details: This study is a prospective, randomized, double-blind clinical trial of individuals with established coronary heart disease.

Study Record Dates

• First Submitted: November 14, 2024
• First Posted: November 15, 2024
• Study Start: April 1, 2026
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): April 1, 2030
• Last Updated: April 14, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)