E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003601 |
E.1.2 | Term | Atherosclerosis |
E.1.2 | System Organ Class | 100000004866 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this clinical trial is to demonstrate the superiority of at least one dose of canakinumab compared to placebo in reducing the risk of recurrent major cardiovascular disease events (cardiovascular death, non-fatal MI and stroke) in a population of clinically stable post-MI patients with elevated hsCRP receiving standard of care. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives:
- To demonstrate superiority of canakinumab compared to placebo on the composite endpoint of CV death, non-fatal MI, stroke, and hospitalization for unstable angina requiring unplanned revascularizations.
- To demonstrate superiority of canakinumab compared to placebo on the endpoint of new onset type 2 diabetes among those with pre-diabetes at randomization
- To demonstrate superiority of canakinumab compared to placebo on the composite endpoint of all-cause mortality, non-fatal MI and stroke.
- To demonstrate superiority of canakinumab as compared to placebo on the endpoint of allcause mortality
- To evaluate the long-term safety of canakinumab therapy in a placebo(standard of care) - controlled setting
- Extension phase: to collect additional long-term safety data on continued exposure to canakinumab in patients who participated in the pivotal phase |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
All patients who suffer a stroke during the double-blind period will participate in the, Post-Stroke Functional
Assessment Sub-Study.
Pre-clinical models indicate that anti-inflammatory therapy and specifically IL-1β blocking therapy may limit the size of stroke impact in brain tissue and facilitate functional recovery has been digitally signed from stroke. Therefore, this clinical trial includes a sub-study on functional assessment of the patients recovering from stroke experienced during this trial and agreeing to participate in this sub-study in order to support the hypothesis that canakinumab therapy facilitates functional recovery from stroke. |
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E.3 | Principal 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 |
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E.4 | Principal 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
Other protocol-defined inclusion/exclusion criteria may apply |
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E.5 End points |
E.5.1 | Primary end point(s) |
Time to first occurrence of a major adverse cardiovascular event, which is a composite endpoint consisting of cardiovascular death, non-fatal MI, and stroke |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Time to first occurrence of a major adverse cardiovascular event, which is a composite endpoint consisting of cardiovascular death, non-fatal MI, and stroke, and hospitalization for unstable angina requiring unplanned revascularization
- Time to new onset of type 2 diabetes among those with pre-diabetes at randomization
- Time to first occurence of non-fatal MI, stroke and all-cause mortality composite
- Time to all-cause mortality |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 14 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 501 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Australia |
Austria |
Belgium |
Brazil |
Bulgaria |
Canada |
China |
Colombia |
Czech Republic |
Estonia |
Germany |
Greece |
Guatemala |
Hungary |
Iceland |
India |
Italy |
Japan |
Korea, Republic of |
Latvia |
Lithuania |
Netherlands |
Norway |
Peru |
Poland |
Romania |
Russian Federation |
Slovakia |
South Africa |
Sweden |
Taiwan |
Turkey |
United Kingdom |
United States |
Venezuela, Bolivarian Republic of |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 8 |
E.8.9.2 | In all countries concerned by the trial months | 6 |