Safety and Efficacy of Multiple Doses of Canakinumab (ACZ... | NCT00581945

Label	Type	Description	Intervention Names
Canakinumab	Experimental	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
Placebo	Placebo Comparator	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

Name	Type	Description	Arm Group Labels	Other Names
Canakinumab	Drug	The dose of canakinumab (ACZ885) administered was individualized, based on the subject's weight pre-dose, and was administered via intravenous infusion.	Canakinumab

Outcomes Module

Primary Outcomes

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.

Secondary Outcomes

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.

Eligibility Module

Eligibility 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.

Name	Affiliation	Role
NOVARTIS	Novartis investigator site	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Novartis Investigator Site		Anaheim	California	92801	United States
Novartis Investigator Site

ID	Title	Description
FG000	Canakinumab	Participants received an initial dose of 1 mg/kg canakinumab 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.
FG001

ID	Title	Description
BG000	Canakinumab	Participants received an initial dose of 1 mg/kg canakinumab 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.
BG001	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.
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG00074 BG00173 BG002147

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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.

The safety population consisted of all randomized patients who received at least one dose of the study drug.

Posted

Mean

Standard Deviation

Liters

Baseline, Week 25 and Week 45

ID	Title	Description
OG000	Canakinumab	Participants received an initial dose of 1 mg/kg canakinumab 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.
OG001	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.

Units	Counts
Participants	OG00074 OG00173

Title

Denominators

Categories

Change from Baseline at Week 25

Title	Measurements
	OG000-0.027± 0.1725 OG001-0.006± 0.2545

Change from Baseline at Week 45

Title	Measurements
	OG000

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.

The safety population consisted of all randomized patients who received at least one dose of the study drug.

Posted

Number

Participants

Adverse events were collected during the 45 week treatment period and the 12 week follow-up period.

ID	Title	Description
OG000	Canakinumab	Participants received an initial dose of 1 mg/kg canakinumab 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.
OG001	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.

Units	Counts

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.

Safety population

Posted

Mean

Standard Deviation

Percent of predicted

Baseline, Week 25 and Week 45

ID	Title	Description
OG000	Canakinumab	Participants received an initial dose of 1 mg/kg canakinumab 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.
OG001	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.

Units	Counts
Participants

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.

Safety population

Posted

Mean

Standard Deviation

liters

Baseline, Week 25 and Week 45

ID	Title	Description
OG000	Canakinumab	Participants received an initial dose of 1 mg/kg canakinumab 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.
OG001	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.

Units	Counts
Participants

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.

Safety population

Posted

Mean

Standard Deviation

liters

Baseline, Week 25 and Week 45

ID	Title	Description
OG000	Canakinumab	Participants received an initial dose of 1 mg/kg canakinumab 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.
OG001	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.

Units	Counts
Participants

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.

Safety population

Posted

Mean

Standard Deviation

L/sec

Baseline, Week 25 and Week 45

ID	Title	Description
OG000	Canakinumab	Participants received an initial dose of 1 mg/kg canakinumab 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.
OG001	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.

Units	Counts
Participants

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute myocardial infarction	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected74 at risk EG0011 affected73 at risk
Angina unstable	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected74 at risk EG0011 affected73 at risk
Atrial fibrillation	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected74 at risk EG0010 affected73 at risk
Coronary artery disease	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected74 at risk EG0011 affected73 at risk
Palpitations	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected74 at risk EG0011 affected73 at risk
Supraventricular tachycardia	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected74 at risk EG0011 affected73 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected74 at risk EG0011 affected73 at risk
Peptic ulcer	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected74 at risk EG0011 affected73 at risk
Chest discomfort	General disorders	MedDRA	Systematic Assessment	EG0000 affected74 at risk EG0011 affected73 at risk
Chest pain	General disorders	MedDRA	Systematic Assessment	EG0001 affected74 at risk EG0011 affected73 at risk
Oedema peripheral	General disorders	MedDRA	Systematic Assessment	EG0000 affected74 at risk EG0011 affected73 at risk
Oral allergy syndrome	Immune system disorders	MedDRA	Systematic Assessment	EG0000 affected74 at risk EG0011 affected73 at risk
Bronchitis	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected74 at risk EG0010 affected73 at risk
Bronchopulmonary aspergillosis	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected74 at risk EG0010 affected73 at risk
Cellulitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected74 at risk EG0011 affected73 at risk
Pneumonia	Infections and infestations	MedDRA	Systematic Assessment	EG0004 affected74 at risk EG0013 affected73 at risk
Pneumonia mycoplasmal	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected74 at risk EG0010 affected73 at risk
Sepsis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected74 at risk EG0010 affected73 at risk
Staphylococcal abscess	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected74 at risk EG0010 affected73 at risk
Staphylococcal infection	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected74 at risk EG0010 affected73 at risk
Drug toxicity	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected74 at risk EG0010 affected73 at risk
Chronic lymphocytic leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected74 at risk EG0010 affected73 at risk
Lung neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected74 at risk EG0010 affected73 at risk
Small cell lung cancer stage unspecified	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected74 at risk EG0010 affected73 at risk
Ureteric cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected74 at risk EG0010 affected73 at risk
Carotid artery stenosis	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected74 at risk EG0010 affected73 at risk
Benign prostatic hyperplasia	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0002 affected74 at risk EG0010 affected73 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected74 at risk EG0011 affected73 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0009 affected74 at risk EG0017 affected73 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected74 at risk EG0011 affected73 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected74 at risk EG0010 affected73 at risk
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0001 affected74 at risk EG0010 affected73 at risk
Swelling face	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected74 at risk EG0011 affected73 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0005 affected74 at risk EG0015 affected73 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected74 at risk EG0014 affected73 at risk
Nausea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0005 affected74 at risk EG0016 affected73 at risk
Vomiting	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0005 affected74 at risk EG0011 affected73 at risk
Pyrexia	General disorders	MedDRA	Systematic Assessment	EG0007 affected74 at risk EG0017 affected73 at risk
Candidiasis	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected74 at risk EG0014 affected73 at risk
Gastroenteritis viral	Infections and infestations	MedDRA	Systematic Assessment	EG0004 affected74 at risk EG0012 affected73 at risk
Oral candidiasis	Infections and infestations	MedDRA	Systematic Assessment	EG0003 affected74 at risk EG0014 affected73 at risk
Sinusitis	Infections and infestations	MedDRA	Systematic Assessment	EG0006 affected74 at risk EG0015 affected73 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0009 affected74 at risk EG0014 affected73 at risk
Urinary tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0004 affected74 at risk EG0014 affected73 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0005 affected74 at risk EG0014 affected73 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG00038 affected74 at risk EG00136 affected73 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0008 affected74 at risk EG0016 affected73 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected74 at risk EG0014 affected73 at risk
Hypertension	Vascular disorders	MedDRA	Systematic Assessment	EG0004 affected74 at risk EG0011 affected73 at risk

ID	Term
D008173	Lung Diseases, Obstructive
D008171	Lung Diseases
D012140	Respiratory Tract Diseases
D002908	Chronic Disease
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Canakinumab	Participants received an initial dose of 1 mg/kg canakinumab 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.			23	74	59	74
EG001	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.			14	73	51	73