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

Active, not recruiting

Phase 3 Results N/A

Trial Description

Main Study (CACZ885M2301): The purpose of the pivotal phase of this trial is to test the hypothesis that canakinumab treatment of patients with MI at least one month prior to study entry and elevated hsCRP will 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 is 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 is 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 increases insulin secretion and insulin sensitivity.

Detailed Description

There will be a seamless transition from the pivotal phase to the extension phase of the main study. LPLV of the pivotal phase will be in 02/2017.

Conditions

Interventions

  • Placebo Drug
    ARM 1: Kind: Experimental
    Label: Placebo
  • Canakinumab Drug
    ARM 1: Kind: Experimental
    Label: Canakinumab Dose 1
    ARM 2: Kind: Experimental
    Label: Canakinumab Dose 2
    ARM 3: Kind: Experimental
    Label: Canakinumab Dose 3
    ARM 4: Kind: Experimental
    Label: Canakinumab 50 mg
    Description: Description: Canakinumab 50 mg quarterly subcutaneous + standard of care therapy.
    ARM 5: Kind: Experimental
    Label: Canakinumab Dose 150 mg
    Description: Description: Canakinumab 150 mg quarterly subcutaneous + standard of care therapy.
    ARM 6: Kind: Experimental
    Label: Canakinumab Dose 300 mg
    Description: Description: Canakinumab 150 mg quarterly subcutaneous + standard of care therapy.
    ARM 7: Kind: Experimental
    Label: Canakinumab Dose 50 mg
    Description: Pivotal Phase: Blinded Canakinumab 50 mg quarterly subcutaneous + standard of care therapy. Extension Phase: Blinded canakinumab 50 mg quarterly subcutaneous + standard of care therapy, switched to open-label canakinumab 150 mg quarterly subcutaneous + standard of care therapy after 9 months.

Trial Design

  • Allocation: Randomized
  • Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
  • Purpose: Treatment
  • Endpoint: Safety/Efficacy Study
  • Intervention: Parallel Assignment

Outcomes

Type Measure Time Frame Safety Issue
Primary Time to first occurrence of a major adverse cardiovascular event, which is a composite endpoint consisting of cardiovascular death, non-fatal MI, and stroke. 36 Months No
Secondary Time to the first occurrence of the composite cardiovascular endpoint consisting of cardiovascular death, non-fatal MI, stroke, and hospitalization for unstable angina requiring unplanned revascularization. 36 Months No
Secondary Time to new onset type 2 diabetes among those with pre-diabetes at randomization. 36 Months No
Secondary Time to first occurrence of non-fatal MI, stroke, and all-cause mortality composite. 36 Months No
Secondary Time to all-cause mortality. 36 Months No
Primary Time to first occurrence of a major adverse cardiovascular event, which is a composite endpoint consisting of cardiovascular death, non-fatal MI, and stroke 36 months No
Secondary Time to the first occurrence of the composite cardiovascular endpoint consisting of cardiovascular death, non-fatal MI, stroke, and hospitalization for unstable angina requiring unplanned revascularization 36 months No
Secondary Time to new onset type 2 diabetes among those with pre-diabetes at randomization 36 months No
Secondary Time to first occurrence of non-fatal MI, stroke, and all-cause mortality composite 36 months No
Secondary Time to all-cause mortality 36 months No
Primary Main:Time to first occurrence of major adverse cardiovascular event, which is a composite of CV death, non-fatal MI, and stroke. 36 months No
Primary Substudy 1; Change from baseline in carotid plaque burden in the bifurcation region of the index carotid artery 36 months No
Primary Substudy 2; 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 yearly visits. 36 months No
Secondary Main:Time to first occurrence of the composite cardiovascular endpoint consisting of cardiovascular death, non-fatal MI, stroke and hospitalization for unstable angina requiring unplanned revascularization. 36 months No
Secondary Main:Time to new onset type 2 diabetes among patients with pre-diabetes at randomization. 36 months No
Secondary Main:Time to first occurrence of non-fatal MI, stroke and all-cause mortality composite. 36 months No
Secondary Main: Time to all-cause mortality. 36 months No
Secondary Substudy 1; Change from baseline of the total vessel wall area at Month 3 of the index carotid artery. 36 months No
Secondary Substudy 1; Mean total vessel wall area across the left and right carotid artery at Month 3 and Month 24. 36 months No
Secondary Substudy 1; Change from baseline in corresponding total vessel wall area in the left and right carotid arteries. 36 months No
Secondary Substudy 1; The existence of a baseline total vessel wall area by treatment interaction as well as the consistency of the treatment effect across subgroups. 36 months No
Secondary Substudy 2; Change from baseline in insulin sensitivity index. 36 months No
Secondary Substudy 2; 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. 36 months No
Secondary Substudy 2; Change from baseline in fasting pro-insulin concentration /insulin concentration ratio. 36 months No
Secondary Substudy 2; Change from baseline in OGTT stimulated area under the curve (AUC) 0-120 min of C-peptide concentration. 36 months No

Sponsors