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

Purpose

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

Condition	Intervention	Phase
Chronic Obstructive Pulmonary Disease	Drug: Canakinumab Drug: Placebo	Phase 1 Phase 2

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

Resource links provided by NLM:

MedlinePlus related topics: COPD (Chronic Obstructive Pulmonary Disease)

Drug Information available for: Canakinumab

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) [ Time Frame: Baseline, Week 25 and Week 45 ] [ Designated as safety issue: No ]
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.
Change From Baseline in Forced Expiratory Volume in 1 Second Percent Predicted [ Time Frame: Baseline, Week 25 and Week 45 ] [ Designated as safety issue: No ]
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.
Change From Baseline in Forced Vital Capacity (FVC) [ Time Frame: Baseline, Week 25 and Week 45 ] [ Designated as safety issue: No ]
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.
Change From Baseline in Slow Vital Capacity (SVC) [ Time Frame: Baseline, Week 25 and Week 45 ] [ Designated as safety issue: No ]
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.
Change From Baseline in Forced Expiratory Flow 25% to 75% [ Time Frame: Baseline, Week 25 and Week 45 ] [ Designated as safety issue: No ]
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.

Secondary Outcome Measures:

Number of Participants Who Experienced Serious Adverse Events or Discontinued Due to Adverse Events [ Time Frame: Adverse events were collected during the 45 week treatment period and the 12 week follow-up period. ] [ Designated as safety issue: No ]
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.

Enrollment:	147
Study Start Date:	January 2007
Study Completion Date:	May 2010
Primary Completion Date:	May 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.

Eligibility

Ages Eligible for Study:	40 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00581945

Locations

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

Sponsors and Collaborators

Novartis

Investigators

Principal Investigator:

NOVARTIS

Novartis investigator site

More Information

No publications provided

Responsible Party:	External Affairs, Novartis
ClinicalTrials.gov Identifier:	NCT00581945 History of Changes
Other Study ID Numbers:	CACZ885B2204
Study First Received:	December 21, 2007
Results First Received:	May 26, 2011
Last Updated:	June 28, 2011
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Lung Diseases
Respiration Disorders
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Respiratory Tract Diseases

Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 19, 2013