Safety & Effectiveness on Vascular Structure and Function of ACZ885 in Atherosclerosis and Either T2DM or IGT Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00995930
First received: October 15, 2009
Last updated: June 1, 2015
Last verified: June 2015

October 15, 2009
June 1, 2015
December 2009
February 2014   (final data collection date for primary outcome measure)
  • Number of Participants With Adverse Events, Serious Adverse Events and Death [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Participants were monitored for adverse events, serious adverse events and death throughout the study.
  • Change From Baseline in Aortic Distensibility [ Time Frame: baseline, 3 months, 12 months ] [ Designated as safety issue: No ]
    Two axial, ECG-gated, steady state free precession (SSFP) 'cine' images were acquired during breath-hold to determine aortic distensibility. The first image was obtained at the level of the right pulmonary artery through the ascending and proximal descending aorta and the second through the distal aorta below the diaphragm. Imaging of the aorta also enabled evaluation of the plaque burden and additional vascular function measures.
  • Change From Baseline in Plaque Burden (Aortic Vessel Wall Area and Carotid Vessel Wall Area) [ Time Frame: baseline, 3 months, 12 months ] [ Designated as safety issue: No ]
    For assessment of atherosclerotic plaque burden of the aorta, vessel wall images of the aorta were acquired with an ECG gated double-inversion recovery (black blood) fast spin echo sequence applied breath-holding. Using an oblique sagittal image of the aorta as a pilot, serial axial images were acquired to cover a section of the descending thoracic aorta. The midpoint of the right pulmonary artery in cross section was used as the anatomical reference for the first slice in baseline and follow-up scans. For assessment of the atherosclerotic plaque burden in the carotids, vessel wall images were acquired with an axial ECG gated PD (proton density) weighted black blood sequence. The carotid bifurcation was used as the anatomical reference for all three imaging time points (baseline, 12 weeks, 48 weeks) with axial slice planes acquired below the bifurcation region. The mean values reported here for the carotid are reported for the proximal common carotid region.
Measure: Safety, tolerability, and effect of monthly sc administration of ACZ885 on an integrated analysis of vascular function in subjects with atherosclerosis and T2DM or IGT [ Time Frame: 12 weeks and 48 weeks ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00995930 on ClinicalTrials.gov Archive Site
  • Change From Baseline in Pulse Wave Velocity and Pulse Wave Velocity Error [ Time Frame: baseline, 3 months, 12 months ] [ Designated as safety issue: No ]
    Utilizing the SphygmoCor Device, ECG leads placed at the carotid and femoral arteries provided the measure of the pulse wave at that particular arterial location. The distance between the two vascular beds divided by the pulse wave time shift provided a measure of the pulse wave velocity.
  • Change From Baseline in Plaque Composition [ Time Frame: baseline, 3 months, 12 months ] [ Designated as safety issue: No ]
    During the carotid MRI acquisition, in addition to the PD weighted ECG gated double inversion fast spin echo sequences T1 and T2 weighted sequences were acquired. In combination with the PD weighted images, the multi-contrast images were analyzed to determine regions of interest with contrast patterns consistent with the presence of necrotic lipid core, calcification and fibrous tissue in participants who had complex carotid plaque present in the bifurcation region.
  • Change From Baseline in Aortic Strain [ Time Frame: baseline, 3 months, 12 months ] [ Designated as safety issue: No ]
    Arterial strain was computed directly from the cine SSFP images and the change in lumen diameters over the cardiac cycle. The value was independent of pulse pressure and is unitless ratio derived from the maximum to minimum lumen diameters diastole and systole, respectively..
  • Change From Baseline in High Sensitivity C-reactive Protein (hsCRP) [ Time Frame: baseline, 3 months, 12 months ] [ Designated as safety issue: No ]
    Blood samples were collected to analyze hsCRP.
  • Change From Baseline in Fasting Plasma Glucose [ Time Frame: baseline, 3 months, 12 months ] [ Designated as safety issue: No ]
    Blood samples were collected to analyze fasting plasma glucose.
  • Change From Baseline in Hemoglobin A1c (HbA1c) [ Time Frame: baseline, 3 months, 12 months ] [ Designated as safety issue: No ]
    Blood samples were collected to analyze HbA1c.
  • Change From Baseline in 2 Hour Glucose Post Oral Glucose Tolerance Test (OGTT) [ Time Frame: baseline, 3 months, 12 months ] [ Designated as safety issue: No ]
    Blood samples were collected to analyze the 2 hour glucose post OGTT.
  • Change From Baseline in Beta Cell Function (HOMA-B) [ Time Frame: baseline, 3 months, 12 months ] [ Designated as safety issue: No ]
    Blood samples were collected to analyze beta cell function. Beta cell function was calculated by the Homeostasis Model Assessments (of beta cell function (HOMA-B) as follows: HOMA-B: The product of 20 and basal insulin (µU/mL) levels divided by the value of basal glucose (mmol/L) concentrations minus 3.5 [i.e., HOMA-B = 20*basal insulin/(basal glucose-3.5)].
  • Change From Baseline Insulin Resistance (HOMA-IR) [ Time Frame: baseline, 3 months, 12 months ] [ Designated as safety issue: No ]
    Blood samples were collected to analyze insulin resistance. Insulin resistance was calculated by the Homeostasis Model Assessments of insulin resistance (HOMA-IR)) as follows: HOMA-IR: The product of basal glucose (mmol/L) and insulin (µU/mL) levels divided by 22.5 [i.e., HOMA-IR = basal glucose*basal insulin/22.5].
  • Pharmacokinetics: ACZ885 Serum Concentrations [ Time Frame: pre-dose, 0.167 day post dose 1, 7 days post dose 1, 14 days post dose 1, every 30 days post each dose from doses 1 through 12, 60 days post dose 12, 90 days post dose 12 ] [ Designated as safety issue: No ]
    Blood samples were collected to analyze the ACZ885 serum concentrations.
  • Measure: Assess the effect of ACZ885 on aortic pulse wave velocity, plaque composition, arterial strain [ Time Frame: 12 weeks and 48 weeks ] [ Designated as safety issue: No ]
  • Evaluate the effect of ACZ885 on hsCRP [ Time Frame: 12 weeks and 48 weeks ] [ Designated as safety issue: No ]
  • Assess the pharmacokinetics of ACZ885 in patients with atherosclerosis [ Time Frame: 12 weeks and 48 weeks ] [ Designated as safety issue: No ]
  • Assess the effect of ACZ885 on glycemic parameters, including HbA1c and peak glucose levels 2 hours post the administration of an OGTT [ Time Frame: 12 weeks and 48 weeks ] [ Designated as safety issue: No ]
  • Assess the effect of ACZ885 on beta cell function and insulin resistance [ Time Frame: 12 weeks and 48 weeks ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Safety & Effectiveness on Vascular Structure and Function of ACZ885 in Atherosclerosis and Either T2DM or IGT Patients
A Multi-center, Randomized , Double Blind, Placebo-controlled, Study of the Safety, Tolerability, and Effects on Arterial Structure and Function of ACZ885 in Patients With Clinically Evident Atherosclerosis and Either T2DM or IGT

This study will evaluate the effect of ACZ885 on vascular function in patients with documented atherosclerotic disease and T2DM or IGT.

Not Provided
Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Diabetes Mellitus, Type 2
  • Atherosclerosis
  • Prediabetic State
  • Drug: ACZ885
    ACZ885 150 mg was administered subcutaneously once a month for 12 months.
    Other Name: Canakinumab
  • Drug: Placebo
    Matching placebo to ACZ885 was administered subcutaneously once a month for 12 months.
  • Placebo Comparator: Placebo
    subcutaneous (SQ) monthly
    Intervention: Drug: Placebo
  • Experimental: ACZ885
    150 mg SQ monthly
    Intervention: Drug: ACZ885
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
189
February 2014
February 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients with known atherosclerotic disease and documented diagnosis of T2DM for ≤ 14 years OR IGT
  • HbA1c between 6.0% and 10.0%
  • On stable statin therapy or statin intolerant
  • Patients who are eligible and able to participate in the study

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

Other protocol-defined inclusion/exclusion criteria may apply

Both
18 Years to 74 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada,   Germany,   Israel,   United Kingdom
 
NCT00995930
CACZ885I2206, 2009-014618-80
Yes
Novartis ( Novartis Pharmaceuticals )
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
June 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP