Safety, Tolerability and Efficacy of ACZ885 on Leg Artery Structure in Patients With Peripheral Artery Disease

• ClinicalTrials.gov Identifier: NCT01731990
• Recruitment Status: Terminated
• First Posted: November 22, 2012
• Results First Posted: August 22, 2017
• Last Update Posted: December 30, 2020
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

Brief Summary:

This study was designed to assess the safety, tolerability and efficacy of ACZ885 on the leg artery structure and physical activity in patients with atherosclerotic peripheral artery disease and leg pain from walking.

Condition or disease	Intervention/treatment	Phase
Peripheral Artery Disease	Drug: Canakinumab (ACZ885); Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 38 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Double-blind, Placebo-controlled Study of the Safety, Tolerability and Effects on Arterial Structure and Function of ACZ885 in Patients With Intermittent Claudication.
• Actual Study Start Date: October 30, 2012
• Actual Primary Completion Date: August 4, 2016
• Actual Study Completion Date: August 4, 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: Canakinumab (ACZ885); Monthly subcutaneous doses of Canakinumab 150 mg/1 mL for 12 months	Drug: Canakinumab (ACZ885); Dosage form: solution for injection Strength: 150 mg/1 mL Mode of administration: subcutaneous use.
Placebo Comparator: Placebo; Monthly subcutaneous doses of placebo of Canakinumab 150 mg/1 mL for 12 months	Drug: Placebo; Matching placebo of Canakinumab

Outcome Measures

Primary Outcome Measures :

1. Mean Vessel Wall Area Ratio of 12 Months to Baseline [ Time Frame: Baseline, 12 months post-dose ]
   Peripheral artery wall area (superficial femoral artery) measured using Magnetic Resonance Imaging (MRI) cross-section slices. Mean vessel wall area (mm^2) was derived by converting total plaque volume (TPV) (mL) of the vessel to mm^3 by multiplying by 1000, dividing by the number of slices used for the volume calculation, and dividing by the thickness of a slice (3 mm). Least squares mean for ratio of 12 months to baseline was measured from repeated measures mixed effect model with visit, treatment, the treatment-by-visit interaction, baseline and the visit-by-baseline interaction as fixed effects.

Secondary Outcome Measures :

1. Number of Patients With Adverse Events in 12 Months [ Time Frame: Baseline to 12 months post-dose ]
   Summary statistics on adverse event is reported. It is categorized as number of patients in total adverse events (non serious and serious AEs), serious adverse event, death.
2. Serum Amyloid A (SAA) Level Ratio of 12 Months to Baseline [ Time Frame: Baseline, 12 months post-dose ]
   Least squares mean for ratio of 12 months to baseline was measured from repeated measures mixed effect model with visit, treatment, treatment-by-visit interaction, baseline and the visit-by-baseline interaction as fixed effects.
3. High Sensitivity C-reactive Protein (hsCRP) Ratio of 12 Months to Baseline [ Time Frame: Baseline, 12 months post-dose ]
   Least squares mean for ratio of 12 months to baseline was measured from repeated measures mixed effect model with visit, treatment, treatment-by-visit interaction, baseline and the visit-by-baseline interaction as fixed effects.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Key Inclusion Criteria:

• Must have a signed informed consent form.
• Must be between the ages of 18 and 85
• Must experience leg pain associated with walking and have an ankle brachial index between 0.40 and 0.9
• Must be on stable aspirin and statin doses for at least 6 weeks
• Blood pressure within ranges specified in the protocol
• Able to communicate well with the Investigator and understand and comply with the study procedures

Key Exclusion Criteria:

• Recent use of any other experimental drugs
• Pregnant or nursing women
• Women of child bearing potential unless willing to use contraception as detailed in the protocol
• Cannot walk 15 meters (50 feet)
• People on restricted medications as listed in the protocol
• Any open or non-healing wounds with 3 months of study start or infection within 2 weeks or study start
• Significant heart disease
• Uncontrolled diabetes
• Significant kidney or liver disease
• Live vaccinations within 3 months of study start
• History of untreated tuberculosis or active tuberculosis (TB)
• Patients with metal in their body (excluded due to MRI scan) as detailed in the protocol.

Contacts and Locations

Locations

United States, Arizona

Novartis Investigative Site

Phoenix, Arizona, United States, 85302

United States, Florida

Novartis Investigative Site

Jacksonville, Florida, United States, 32207

Novartis Investigative Site

Jacksonville, Florida, United States, 32216

United States, Illinois

Novartis Investigative Site

Chicago, Illinois, United States, 60611

United States, Maryland

Novartis Investigative Site

Lutherville, Maryland, United States, 21093

United States, Ohio

Novartis Investigative Site

Columbus, Ohio, United States, 43215

United States, Tennessee

Novartis Investigative Site

Knoxville, Tennessee, United States, 37920

United States, Virginia

Novartis Investigative Site

Richmond, Virginia, United States, 23294

Germany

Novartis Investigative Site

Hamburg, Germany, 20099

Novartis Investigative Site

Hamburg, Germany, 22559

Novartis Investigative Site

Heidelberg, Germany, 69120

Novartis Investigative Site

Mainz, Germany, 55116

Novartis Investigative Site

München, Germany, 80336

Jordan

Novartis Investigative Site

Amman, Jordan, 11941

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

More Information

Additional Information:

A Plain Language Trial Summary is available on novartisclinicaltrials.com 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Russell KS, Yates DP, Kramer CM, Feller A, Mahling P, Colin L, Clough T, Wang T, LaPerna L, Patel A, Lawall H, Shennak MM, Fulmer J, Nikol S, Smith WB, Müller OJ, Ratchford EV, Basson CT. A randomized, placebo-controlled trial of canakinumab in patients with peripheral artery disease. Vasc Med. 2019 Oct;24(5):414-421. doi: 10.1177/1358863X19859072. Epub 2019 Jul 5.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01731990
• Other Study ID Numbers: CACZ885M2201; 2012-001427-12
• First Posted: November 22, 2012
• Results First Posted: August 22, 2017
• Last Update Posted: December 30, 2020
• Last Verified: March 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

Peripheral artery disease; Intermittent claudication; magnetic resonance imaging

Additional relevant MeSH terms:

Peripheral Arterial Disease; Intermittent Claudication; Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases