Safety and Efficacy of Multiple Doses of Canakinumab (ACZ885) in Chronic Obstructive Pulmonary Disease (COPD) Patients

A Randomized, Double-blind, Placebo Controlled, Exploratory Study to Assess the Safety and Efficacy of Multiple Doses of ACZ885 in Chronic Obstructive Pulmonary Disease (COPD) Patients

Was to evaluate the safety, tolerability and efficacy of multiple doses of canakinumab (ACZ885) vs. placebo when administered via intravenous infusion (IV), on pulmonary function in patients with COPD

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: Canakinumab; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 147
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Anaheim, California, United States, 92801
      • Novartis Investigator Site
    • Los Angeles, California, United States, 90095
      • Novartis Investigator Site
  • Florida
    • Panama City, Florida, United States, 32405
      • Novartis Investigator Site
  • Georgia
    • Marietta, Georgia, United States, 300060
      • Novartis Investigator Site
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Novartis Investigator Site
  • Michigan
    • Livonia, Michigan, United States, 48152
      • Novartis Investigator Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55402
      • Novartis Investigator Site
  • Nebraska
    • Omaha, Nebraska, United States, 68198-5885
      • Novartis Investigator Site
  • New York
    • Buffalo, New York, United States, 14215
      • Novartis Investigator Site
  • South Carolina
    • Spartanburg, South Carolina, United States, 29303
      • Novartis Investigator Site
  • Virginia
    • Richmond, Virginia, United States, 23225
      • Novartis Investigator Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and/or female subjects from 40-80 years (inclusive) of age
• Subjects have a clinical diagnosis of COPD
• Smokers or Ex-smokers with a smoking history of at least 20 pack years
• Post-bronchodilator forced expiratory volume in 1 second (FEV1 ) at screening ≤ 50% of the predicted normal value
• Post-bronchodilator FEV1/FVC ratio < 70%
• History of at least one treated exacerbation during the 24 months year prior to screening or C-Reactive Protein (CRP) ≥3.47 mg/L,
• Subjects should have no concomitant other lung disease or significant concomitant medical conditions that would affect the subjects' safety when participating in the study, or that would be expected to impact on the results of the study
• Female subjects must have been surgically sterilized at least 6 months prior to screening or must be using two forms of contraception, or postmenopausal women
• Able to provide written informed consent prior to study participation.
• Able to communicate well with the investigator and comply with the requirements of the study.

Exclusion Criteria:

• COPD exacerbation(s) requiring treatment within 4 weeks prior to first dosing
• History of lung reduction surgery
• Any undiagnosed nodule on chest x-ray
• Presence of certain medical conditions as specified by the protocol
• Subjects requiring oral or parenteral corticosteroids equivalent to > 10 mg/day or > 20 mg every other day of prednisone or prednisolone
• Documented homozygous alpha-1 antitrypsin deficiency.
• Participation in any clinical investigation within 4 weeks prior to dosing or longer if required by local regulation.
• Donation or loss of 400 mL or more of blood within 8 weeks prior to dosing.
• A past medical history of clinically significant electrocardiogram (ECG) abnormalities or a family history of a prolonged QT-interval syndrome.
• A known hypersensitivity to drugs similar to the study drug.
• History of immunocompromise, including a positive HIV test result.
• A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result.
• History of drug or alcohol abuse within the 12 months prior to screening or evidence of such abuse as indicated by the laboratory assays conducted during screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Canakinumab; Participants received an initial dose of 1 mg/kg canakinumab (ACZ885) via intravenous infusion. Four weeks later, participants received a dose of 3 mg/kg canakinumab, and another dose of 3 mg/kg two weeks later. Thereafter, participants received doses of 6 mg/kg every four weeks until completion of the 45-week treatment period.	Drug: Canakinumab; The dose of canakinumab (ACZ885) administered was individualized, based on the subject's weight pre-dose, and was administered via intravenous infusion.
Placebo Comparator: Placebo; Participants received a matching placebo intravenous infusion at weeks 1, 5, 7, and thereafter every four weeks until completion of the 45-week treatment period.	Drug: Placebo; Matching placebo to ACZ885 administered via intravenous infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)	Forced expiratory volume in 1 second (FEV1) is the amount of air that can be exhaled in one second. FEV1 was measured by spirometry performed at approximately the same time of day on each visit to avoid diurnal variation. All spirometry calibrations and evaluations followed the recommendations of the American Thoracic Society / European Respiratory Society guidelines for acceptability. A positive change from baseline in FEV1 indicates improvement in lung function.	Baseline, Week 25 and Week 45
Change From Baseline in Forced Expiratory Volume in 1 Second Percent Predicted	The FEV1 percent predicted expresses FEV1 as a percentage of the "predicted values" for participants of similar characteristics (height, age, sex, and sometimes race and weight). A positive change from baseline in FEV1 % predicted indicates improvement in lung function.	Baseline, Week 25 and Week 45
Change From Baseline in Forced Vital Capacity (FVC)	Forced Vital Capacity is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. FVC was assessed by spirometry. A positive change from baseline in FVC indicates improvement in lung function.	Baseline, Week 25 and Week 45
Change From Baseline in Slow Vital Capacity (SVC)	Vital Capacity is the amount of air that can be forcibly exhaled from the lungs after a full inhalation. Slow Vital Capacity (SVC) test is performed by having the patient slowly and completely blow out all of the air from their lungs. A positive change from baseline in SVC indicates improvement in lung function.	Baseline, Week 25 and Week 45
Change From Baseline in Forced Expiratory Flow 25% to 75%	The forced expiratory flow (FEF) 25%-75% measurement describes the amount of air expelled from the lungs during the middle half (25% - 75%) of the forced vital capacity test and is measured using spirometry. A positive change from baseline in FEF indicates improvement in lung function.	Baseline, Week 25 and Week 45

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Experienced Serious Adverse Events or Discontinued Due to Adverse Events	Safety was assessed by the number of participants with serious adverse events and/or adverse events leading to study discontinuation. A summary of adverse events is presented with this outcome, additional details are provided in the Adverse Events section.	Adverse events were collected during the 45 week treatment period and the 12 week follow-up period.

Collaborators and Investigators

• Sponsor: Novartis

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Actual): May 1, 2010
• Study Completion (Actual): May 1, 2010

Study Registration Dates

• First Submitted: December 21, 2007
• First Submitted That Met QC Criteria: December 21, 2007
• First Posted (Estimate): December 28, 2007

Study Record Updates

• Last Update Posted (Estimate): June 30, 2011
• Last Update Submitted That Met QC Criteria: June 28, 2011
• Last Verified: June 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: CACZ885B2204