Cardiovascular Risk Reduction Study (Reduction in Recurrent Major CV Disease Events) (CANTOS)

Novartis

Status and phase: Completed; Phase 3

Conditions: Atherosclerosis

Treatments: Drug: Placebo; Drug: Canakinumab; Drug: Standard of care

Study type: Interventional

Funder types: Industry

Identifiers

NCT01327846

CACZ885M2301

2010-022970-14 (EudraCT Number)

Details and patient eligibility

About

Main Study (CACZ885M2301): The purpose of the pivotal phase of this trial was to test the hypothesis that canakinumab treatment of patients with myocardial infarction (MI) at least one month prior to study entry and elevated hsCRP could prevent recurrent cardiovascular events.

The purpose of the extension phase of the main study is to collect additional long-term safety data on continued exposure to canakinumab in patients who participated in the pivotal phase.

Sub-study 1 (CACZ885M2301S1): The purpose of this sub-study was to evaluate the effect of quarterly subcutaneous canakinumab treatment for 24 months comparted with placebo on the carotid plaque burden measured by integrated vascular MRI in patients enrolled in the CACZ885M2301 study (CANTOS).

Sub-study 2 (CACZ885M2301S2): The purpose of this CANTOS sub-study was to determine whether, in patients with type 2 diabetes participating in the CANTOS main study, canakinumab compared to placebo, on top of standard of care could increase insulin secretion and insulin sensitivity.

Full description

Sub-study 1 and 2 were terminated prior to data collection from subjects. However, there is an ongoing extension trial where patients are receiving open-drug label.

Enrollment: 10,066 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Main Study Inclusion Criteria:

• Written informed consent
• Male, or Female of non-child-bearing potential
• Age ≥ 18 years.
• Spontaneous MI at least 30 days before randomization. hsCRP ≥ 2 mg/L

Substudy 1 Inclusion:

• All Inclusion from Main Study
• Acquisition of evaluable baseline MRI images of bilateral carotid arteries by the imaging core laboratory

Substudy 2 Inclusion:

• All inclusion from Main Study
• T2D at baseline per Main protocol criteria and be on a stable anti-hyperglycemic medication for at least 4 weeks prior to the baseline OGTT test
• Willing to have the OGTT assessment started before 10 am

Main Study Exclusion Criteria:

• Pregnant or nursing (lactating) women
• Women of child-bearing potential
• Any of the following concomitant diseases
• Planned coronary revascularization (PCI or CABG)
• Major non-cardiac surgical or endoscopic procedure within past 6 months
• Multi-vessel CABG surgery within the past 3 years
• Symptomatic patients with Class IV heart failure (HF) (New York Heart Association [NYHA].
• Uncontrolled hypertension
• Uncontrolled diabetes
• History or evidence of active tuberculosis (TB) infection Substudy 1 Exclusion
• All Main exclusion
• Patients with prior history of carotid angioplasty, stenting, or carotid atherectomy
• Patients with contraindications to MRI examination (brain aneurysm clip, implanted neural stimulator, implanted cardiac pacemaker, pacemaker wires or defibrillator, prosthetic heart valves, cochlear implant, ocular foreign body or other implanted body, tattoos, implanted insulin pump, metal shrapnel or bullet)
• Patients prone to claustrophobia or known anxiety disorders
• BMI > 40 kg/m2 Substudy 2 Exclusion
• This sub-study does not have any additional exclusion criteria.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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10,066 participants in 4 patient groups, including a placebo group

Canakinumab Dose 50 mg

Experimental group

Description:

Pivotal Phase: Blinded Canakinumab 50 mg quarterly subcutaneous + standard of care therapy. Extension Phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care therapy

Treatment:

Drug: Canakinumab

Drug: Standard of care

Canakinumab Dose 150 mg

Experimental group

Description:

Pivotal Phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care therapy

Treatment:

Drug: Canakinumab

Drug: Standard of care

Canakinumab Dose 300 mg

Experimental group

Description:

Pivotal Phase: Blinded Canakinumab 300 mg quarterly subcutaneous (with one additional dose at week 2) + standard of care therapy. Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care therapy

Treatment:

Drug: Canakinumab

Drug: Standard of care

Placebo

Placebo Comparator group

Description:

Pivotal Phase: Blinded matching placebo quarterly subcutaneous + standard of care therapy. Extension Phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care therapy

Treatment:

Drug: Placebo

Drug: Standard of care