Phase 3 N=10,061 Randomized Triple-blind Treatment

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

Atherosclerosis

Bottom Line

View on ClinicalTrials.gov: NCT01327846 ↗

Enrolled (actual)

10,061

Serious AEs

28.4%

Results posted

Jan 2020

Primary outcome: Primary: Analysis of Core Phase First CEC Confirmed Major Adverse Cardiovascular Events (MACE) and Its Components — 322; 320; 313; 535 Participants — p=0.0648

Study Design & Population

Study type: Interventional
Phase: Phase 3
Interventions: Canakinumab (Drug); Placebo (Drug); Standard of care (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: Novartis Pharmaceuticals
Primary completion: Mar 2017

Outcome Measures

Outcome	Result	p-value
PRIMARY Analysis of Core Phase First CEC Confirmed Major Adverse Cardiovascular Events (MACE) and Its Components	322; 320; 313; 535; 151; 144	0.0648
PRIMARY Substudy 1 (Core Phase): Change From Baseline in Carotid Plaque Burden in the Bifurcation Region of the Index Carotid Artery	—	—
PRIMARY Substudy 2 (Core Phase): Change From Baseline of the Insulin Secretion Rate (ISR) Relative to Glucose 0-30 Min Defined as Φ30 = AUCISR 0-30 / AUCGluc 0-30 Averaged Across the Year 3, 4, 5 Visits	—	—
SECONDARY Patients With Core Phase CEC Confirmed CV Death, Non-fatal MI, Non-fatal Stroke, or Hospitalization for Unstable Angina Requiring Unplanned Revascularization	348; 352; 344; 601; 34; 38	0.0648
SECONDARY Patients With Core Phase New Onset Type 2 Diabetes Among Patients With Pre-diabetes at Randomization	169; 171; 161; 246	0.8456
SECONDARY Core Phase All-cause Mortality, Non-fatal MI, or Non-fatal Stroke	403; 395; 394; 661	0.028 sig
SECONDARY Core Phase All-cause Mortality	239; 238; 228; 375	0.406
SECONDARY Summary of Adverse Events (Core Phase)	1987; 1970; 1872; 2915; 355; 350	—
SECONDARY Summary of Adverse Events (Extension Phase)	788; 845; 793; 1250; 40; 34	—
SECONDARY Substudy 1 (Core Phase): Change From Baseline of the Total Vessel Wall Area at Month 3 in the Bifurcation Region of the Index Carotid Artery	—	—
SECONDARY Substudy 1 (Core Phase): Mean Total Vessel Wall Area Across the Left and Right Carotid Artery at Month 3 and Month 24	—	—
SECONDARY Substudy 1 (Core Phase): Change From Baseline in Corresponding Total Vessel Wall Area in the Left and Right Carotid Arteries	—	—
SECONDARY Substudy 1 (Core Phase): The Existence of a Baseline Total Vessel Wall Area by Treatment Interaction as Well as the Consistency of the Treatment Effect Across Subgroups	—	—
SECONDARY Substudy 2 (Core Phase): Change From Baseline in Insulin Sensitivity Index	—	—
SECONDARY Substudy 2 (Core Phase): Change From Baseline in OGTT Stimulated Area Under Curve (AUC) 0-120 Min of Glucose Concentration, Insulin Concentration, Pro-insulin Concentration, and Insulin Concentration/Glucose Concentration Ratio	—	—
SECONDARY Substudy 2 (Core Phase): Change From Baseline in Fasting Pro-Insulin Concentration/Insulin Concentration Ratio	—	—
SECONDARY Substudy 2 (Core Phase): Change From Baseline in OGTT Stimulated Area Under the Curve (AUC) 0-120 Min of C-peptide Concentration	—	—

Summary

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.

Eligibility 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.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01327846). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.