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
  Purpose

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


Condition Intervention Phase
Diabetes Mellitus, Type 2
Atherosclerosis
Prediabetic State
Drug: ACZ885
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 189
Study Start Date: December 2009
Study Completion Date: February 2014
Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
subcutaneous (SQ) monthly
Drug: Placebo
Matching placebo to ACZ885 was administered subcutaneously once a month for 12 months.
Experimental: ACZ885
150 mg SQ monthly
Drug: ACZ885
ACZ885 150 mg was administered subcutaneously once a month for 12 months.
Other Name: Canakinumab

  Eligibility

Ages Eligible for Study:   18 Years to 74 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00995930

Locations
United States, New York
Novartis Investigative Site
New York, New York, United States, 10029
United States, Ohio
Novartis Investigative Site
Cincinnati, Ohio, United States, 45219
Canada, Quebec
Novartis Investigative Site
Montreal, Quebec, Canada, H1T 1C8
Germany
Novartis Investigative Site
Mainz, Germany, 55116
Novartis Investigative Site
Neuss, Germany, 41460
Novartis Investigative Site
Ulm, Germany, 89081
Israel
Novartis Investigative Site
Jerusalem, Israel, 91120
United Kingdom
Novartis Investigative Site
Oxford, UK, United Kingdom, OX2 6HE
Novartis Investigative Site
London, United Kingdom, EC1M 6BQ
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00995930     History of Changes
Other Study ID Numbers: CACZ885I2206, 2009-014618-80
Study First Received: October 15, 2009
Results First Received: January 29, 2015
Last Updated: June 1, 2015
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Germany: Paul-Ehrlich-Institut
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Israel: Ministry of Health

Keywords provided by Novartis:
Atherosclerosis,
Type 2 Diabetes Mellitus, T2DM,
Cardiovascular Diseases, ACZ885, impaired glucose tolerance, IGT, Canakinumab

Additional relevant MeSH terms:
Arteriosclerosis
Atherosclerosis
Diabetes Mellitus
Diabetes Mellitus, Type 2
Prediabetic State
Arterial Occlusive Diseases
Cardiovascular Diseases
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Vascular Diseases

ClinicalTrials.gov processed this record on July 05, 2015