E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
atherosclerosis
type 2 diabetes mellitus (T2DM) |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012594 |
E.1.2 | Term | Diabetes |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003601 |
E.1.2 | Term | Atherosclerosis |
E.1.2 | System Organ Class | 10047065 - Vascular disorders |
|
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 |
-To assess the safety and tolerability of monthly sc administration of ACZ885 in patients with atherosclerosis and type 2 diabetes mellitus (T2DM) or impaired glucose tolerance (IGT)
-To assess the effect of ACZ885 on aortic distensibility, endothelial function and total plaque burden |
|
E.2.2 | Secondary objectives of the trial |
-To assess the effect of ACZ885 on aortic pulse wave velocity, plaque composition and arterial strain
-To evaluate the effect of ACZ885 on hsCRP
-To assess the pharmacokinetics of ACZ885 in patients with atherosclerosis
-To assess the effect of ACZ885 on glycemic parameters, including HbA1c, CPeptide, and peak glucose levels 2 hours post the administration of an OGTT
-To assess the effect of ACZ885 on beta cell function and insulin resistance |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Patients with known atherosclerotic disease and documented diagnosis of T2DM for ≤ 14 years OR IGT
-HbA1c between 6.0% and 10%
-On stable statin therapy or statin intolerant
-Patients who are eligible and able to participate in the study
|
|
E.4 | Principal exclusion criteria |
-Contraindications to MRI
-NYHA class IV Heart Failure
-NYHA class I – III heart failure with acute exacerbation in 3 months prior to screening
-Patients with type 1 diabetes
-Acute infections
-HsCRP > 30 mg/dL
-Aortic aneurysm ≥ 5cm
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
-safety and tolerability of monthly sc administration of ACZ885 in patients with atherosclerosis and type 2 diabetes mellitus (T2DM) or impaired glucose tolerance (IGT)
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
-effect of ACZ885 on aortic pulse wave velocity, plaque composition and arterial strain
-effect of ACZ885 on hsCRP
- pharmacokinetics of ACZ885 in patients with atherosclerosis
-effect of ACZ885 on glycemic parameters, including HbA1c, C-Peptide, and peak glucose levels 2 hours post the administration of an OGTT
-effect of ACZ885 on beta cell function and insulin resistance |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | No |
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 | 2 |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
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 |
Canada |
Germany |
United Kingdom |
United States |
|
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
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |