Diabetes Mellitus, Type 2Phase 2NCT00995930

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

A Phase 2 study testing ACZ885 in people with Diabetes Mellitus, Type 2 and Atherosclerosis, run by Novartis Pharmaceuticals at 9 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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

Who is it for?: Ages 18 to 74 years
Conditions the study is for: Diabetes Mellitus, Type 2, Atherosclerosis, Prediabetic State
What is being tested?: ACZ885
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 189 participants
Where: 9 sitesin 5 countries
Study dates: Dec 2009to Feb 2014
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 74 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

9 sites in 5 countries.

Country

City, postcode or hospital

9 sites in 5 countries

Germany3 sites

Novartis Investigative Site
Mainz, 55116
Novartis Investigative Site
Neuss, 41460
Novartis Investigative Site
Ulm, 89081

Other trials in Germany

United States2 sites

Novartis Investigative Site
Cincinnati, Ohio, 45219
Novartis Investigative Site
New York, New York, 10029

Other trials in United States

United Kingdom2 sites

Novartis Investigative Site
London, EC1M 6BQ
Novartis Investigative Site
Oxford, UK, OX2 6HE

Other trials in United Kingdom

Canada1 site

Novartis Investigative Site
Montreal, Quebec, H1T 1C8

Other trials in Canada

Israel1 site

Novartis Investigative Site
Jerusalem, 91120

Other trials in Israel

About this study

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

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
Being tested: ACZ885, Placebo
Keywords: Atherosclerosis,, Type 2 Diabetes Mellitus, T2DM,, Cardiovascular Diseases, ACZ885, impaired glucose tolerance, IGT, Canakinumab
Medical subject headings: Diabetes Mellitus, Type 2, Atherosclerosis, Prediabetic State, Cardiovascular Diseases, Glucose Intolerance

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ACZ885Drug
Also called Canakinumab
ACZ885 150 mg was administered subcutaneously once a month for 12 months.
PlaceboDrug
Matching placebo to ACZ885 was administered subcutaneously once a month for 12 months.

Study groups in NCT00995930
Study group	Role	What they receive
Placebo	Placebo comparator	subcutaneous (SQ) monthly Receives: Drug: Placebo
ACZ885	Experimental	150 mg SQ monthly Receives: Drug: ACZ885

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: baseline, 3 months, 12 months

Secondary outcomes (10)

Change From Baseline in Pulse Wave Velocity and Pulse Wave Velocity Error
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.
Measured: baseline, 3 months, 12 months
Change From Baseline in Plaque Composition
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.
Measured: baseline, 3 months, 12 months
Change From Baseline in Aortic Strain
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..
Measured: baseline, 3 months, 12 months
Change From Baseline in High Sensitivity C-reactive Protein (hsCRP)
Blood samples were collected to analyze hsCRP.
Measured: baseline, 3 months, 12 months
Change From Baseline in Fasting Plasma Glucose
Blood samples were collected to analyze fasting plasma glucose.
Measured: baseline, 3 months, 12 months
Change From Baseline in Hemoglobin A1c (HbA1c)
Blood samples were collected to analyze HbA1c.
Measured: baseline, 3 months, 12 months
Change From Baseline in 2 Hour Glucose Post Oral Glucose Tolerance Test (OGTT)
Blood samples were collected to analyze the 2 hour glucose post OGTT.
Measured: baseline, 3 months, 12 months
Change From Baseline in Beta Cell Function (HOMA-B)
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)].
Measured: baseline, 3 months, 12 months
Change From Baseline Insulin Resistance (HOMA-IR)
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].
Measured: baseline, 3 months, 12 months
Pharmacokinetics: ACZ885 Serum Concentrations
Blood samples were collected to analyze the ACZ885 serum concentrations.
Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Dec 2009Feb 2014

First posted16 Oct 2009 (estimated)
Study startDec 2009
Primary completionFeb 2014
Study completionFeb 2014

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 189 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00995930
Sponsor's protocol ID: CACZ885I2206
Other IDs: 2009-014618-80, 2009
Status last verified: Jun 2015
First submitted: 15 Oct 2009
Last updated: 29 Jun 2015
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

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.
PubMed 27737744

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 29 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT00995930
Acronym / sponsor ID: CACZ885I2206
Conditions: Diabetes Mellitus, Type 2, Atherosclerosis, Prediabetic State
Keywords: Atherosclerosis,, Type 2 Diabetes Mellitus, T2DM,, Cardiovascular Diseases, ACZ885, impaired glucose tolerance, IGT, Canakinumab
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 189 participants (actual)
Lead sponsor: Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: Dec 2009
Primary completion: Feb 2014 (actual)
Study completion: Feb 2014 (actual)
First posted: 16 Oct 2009 (estimated)
Results: Posted 6 Mar 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Placebo	Placebo comparator	Drug: Placebosubcutaneous (SQ) monthly
ACZ885	Experimental	Drug: ACZ885150 mg SQ monthly

Who may qualify

Ages: 18 to 74 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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

Key exclusion criteria (8 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
ACZ885Also: CanakinumabACZ885 150 mg was administered subcutaneously once a month for 12 months.	Drug	ACZ885
PlaceboMatching placebo to ACZ885 was administered subcutaneously once a month for 12 months.	Drug	Placebo

Primary outcome

Number of Participants With Adverse Events, Serious Adverse Events and Death
Time frame: 12 months
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
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
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.

10 secondary outcomes

Change From Baseline in Pulse Wave Velocity and Pulse Wave Velocity Error
Time frame: baseline, 3 months, 12 months
Change From Baseline in Plaque Composition
Time frame: baseline, 3 months, 12 months
Change From Baseline in Aortic Strain
Time frame: baseline, 3 months, 12 months
Change From Baseline in High Sensitivity C-reactive Protein (hsCRP)
Time frame: baseline, 3 months, 12 months
Change From Baseline in Fasting Plasma Glucose
Time frame: baseline, 3 months, 12 months
Change From Baseline in Hemoglobin A1c (HbA1c)
Time frame: baseline, 3 months, 12 months
Change From Baseline in 2 Hour Glucose Post Oral Glucose Tolerance Test (OGTT)
Time frame: baseline, 3 months, 12 months
Change From Baseline in Beta Cell Function (HOMA-B)
Time frame: baseline, 3 months, 12 months
Change From Baseline Insulin Resistance (HOMA-IR)
Time frame: baseline, 3 months, 12 months
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

Results and safety

Results posted to the registry on 6 Mar 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo	94	73
ACZ885	95	67

Primary outcome: Number of Participants With Adverse Events, Serious Adverse Events and Death

Time frame: 12 months. Number. Unit: Number of participants

Measure	Placebo n = 94	ACZ885 n = 95
Adverse events (serious and non-serious)	80	77
Serious adverse events	14	25
Deaths	0	1

Population analysed: Safety analysis set: The safety analysis set included all randomized participants who received at least one dose of study drug.

Primary outcome: Change From Baseline in Aortic Distensibility

Time frame: baseline, 3 months, 12 months. Least squares mean (Standard Error). Unit: mmHg^-1

Measure	Placebo n = 92	ACZ885 n = 92
3 months, proximal ascending region (n=61,63)	-0.0001 (0.0001)	0.0001 (0.0001)
12 months, proximal ascending region (n=56,55)	-0.0001 (0.0001)	-0.0001 (0.0001)

Population analysed: Only participants from the imaging analysis set, who had evaluable data at both baseline and the given post-baseline time point, were included in the analysis for that post baseline time point. The imaging analysis set included randomized participants who received at least one dose of study medication.

Primary outcome: Change From Baseline in Plaque Burden (Aortic Vessel Wall Area and Carotid Vessel Wall Area)

Time frame: baseline, 3 months, 12 months. Least squares mean (Standard Error). Unit: mm^2

Measure	Placebo n = 92	ACZ885 n = 92
aortic, proximal ascending, 3 months (n=69,62)	14.80 (6.86)	-0.51 (6.62)
aortic, proximal ascending, 12 months (n=61,53)	30.58 (10.46)	8.71 (10.49)
carotid, mean (right and left), 3 months (n=66,59)	1.41 (1.10)	-0.29 (1.12)
carotid, mean (right and left), 12 mos. (n=55,48)	3.50 (1.51)	0.73 (1.48)

10 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
ACZ885 150mg	25 of 95 (26.3%)	46 of 95 (48.4%)	Not reported
Placebo	14 of 94 (14.9%)	65 of 94 (69.1%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 29 Jun 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 27737744Choudhury 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Novartis Pharmaceuticals study director

Novartis Pharmaceuticals

9 sites in 5 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing ACZ885 in people with Diabetes Mellitus, Type 2 and Atherosclerosis, run by Novartis Pharmaceuticals at 9 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in Germany, United States, United Kingdom, Canada, Israel. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Mar 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Adverse Events, Serious Adverse Events and Death (time frame: 12 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00995930, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jun 2015.