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

Chronic Obstructive Pulmonary Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00581945
• Other study ID #: CACZ885B2204
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: December 21, 2007
• Last updated: June 28, 2011
• Start date: January 2007
• Est. completion date: May 2010

Study information

• Verified date: June 2011
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 147
• Est. completion date: May 2010
• Est. primary completion date: May 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years to 80 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

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
Matching placebo to ACZ885 administered via intravenous infusion.

Locations

Country	Name	City	State
United States	Novartis Investigator Site	Anaheim	California
United States	Novartis Investigator Site	Baltimore	Maryland
United States	Novartis Investigator Site	Buffalo	New York
United States	Novartis Investigator Site	Livonia	Michigan
United States	Novartis Investigator Site	Los Angeles	California
United States	Novartis Investigator Site	Marietta	Georgia
United States	Novartis Investigator Site	Minneapolis	Minnesota
United States	Novartis Investigator Site	Omaha	Nebraska
United States	Novartis Investigator Site	Panama City	Florida
United States	Novartis Investigator Site	Richmond	Virginia
United States	Novartis Investigator Site	Spartanburg	South Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Novartis

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Secondary	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.	No