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

NCT00995930 | Completed Phase 2 Results DMC

• 2 other identifiers: CACZ885I22062009-014618-80
• Study Type: interventional
• Target: 189
• Locations: 5 countries
• Sites: 9

Brief Summary

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

Conditions

Diabetes Mellitus, Type 2; Atherosclerosis; Prediabetic State

Keywords

Atherosclerosis,; Type 2 Diabetes Mellitus, T2DM,; Cardiovascular Diseases, ACZ885, impaired glucose tolerance, IGT, Canakinumab

Outcome Measures

Primary Outcomes (3)

• Number of Participants With Adverse Events, Serious Adverse Events and Death

  Participants were monitored for adverse events, serious adverse events and death throughout the study.

  12 months

• Change From Baseline in Aortic Distensibility

  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.

  baseline, 3 months, 12 months

• Change From Baseline in Plaque Burden (Aortic Vessel Wall Area and Carotid Vessel Wall Area)

  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.

  baseline, 3 months, 12 months

Secondary Outcomes (10)

• Change From Baseline in Pulse Wave Velocity and Pulse Wave Velocity Error

  baseline, 3 months, 12 months

• Change From Baseline in Plaque Composition

  baseline, 3 months, 12 months

• Change From Baseline in Aortic Strain

  baseline, 3 months, 12 months

• Change From Baseline in High Sensitivity C-reactive Protein (hsCRP)

  baseline, 3 months, 12 months

• Change From Baseline in Fasting Plasma Glucose

  baseline, 3 months, 12 months

Study Arms (2)

Placebo

PLACEBO COMPARATOR

subcutaneous (SQ) monthly

Drug: Placebo

ACZ885

EXPERIMENTAL

150 mg SQ monthly

Drug: ACZ885

Interventions

ACZ885 DRUG

ACZ885 150 mg was administered subcutaneously once a month for 12 months.

Also known as: Canakinumab

ACZ885

Placebo DRUG

Matching placebo to ACZ885 was administered subcutaneously once a month for 12 months.

Placebo

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (9)

Novartis Investigative Site

New York, New York, 10029, United States

Location

Novartis Investigative Site

Cincinnati, Ohio, 45219, United States

Location

Novartis Investigative Site

Montreal, Quebec, H1T 1C8, Canada

Location

Novartis Investigative Site

Mainz, 55116, Germany

Location

Novartis Investigative Site

Neuss, 41460, Germany

Location

Novartis Investigative Site

Ulm, 89081, Germany

Location

Novartis Investigative Site

Jerusalem, 91120, Israel

Location

Novartis Investigative Site

Oxford, UK, OX2 6HE, United Kingdom

Location

Novartis Investigative Site

London, EC1M 6BQ, United Kingdom

Location

Related Publications (1)

• Choudhury RP, Birks JS, Mani V, Biasiolli L, Robson MD, L'Allier PL, Gingras MA, Alie N, McLaughlin MA, Basson CT, Schecter AD, Svensson EC, Zhang Y, Yates D, Tardif JC, Fayad ZA. Arterial Effects of Canakinumab in Patients With Atherosclerosis and Type 2 Diabetes or Glucose Intolerance. J Am Coll Cardiol. 2016 Oct 18;68(16):1769-1780. doi: 10.1016/j.jacc.2016.07.768.

  PMID: 27737744 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Atherosclerosis; Prediabetic State; Cardiovascular Diseases; Glucose Intolerance

Interventions

canakinumab

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Hyperglycemia

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2009
• First Posted: October 16, 2009
• Study Start: December 1, 2009
• Primary Completion: February 1, 2014
• Study Completion: February 1, 2014
• Last Updated: June 29, 2015
• Results First Posted: March 6, 2015

Record last verified: 2015-06

Locations

IL (1); GB (2); US (2); DE (3); CA (1)