Trial Outcomes & Findings for Safety and Efficacy of Multiple Doses of Canakinumab (ACZ885) in Chronic Obstructive Pulmonary Disease (COPD) Patients (NCT NCT00581945)

NCT ID: NCT00581945

Last Updated: 2011-06-30

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 147 participants
• Primary outcome timeframe: Baseline, Week 25 and Week 45
• Results posted on: 2011-06-30

Participant Flow

Participant milestones

Measure	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.	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.
Overall Study STARTED	74	73
Overall Study COMPLETED	65	63
Overall Study NOT COMPLETED	9	10

Reasons for withdrawal

Measure	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.	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.
Overall Study Adverse Event	4	4
Overall Study Unsatisfactory therapeutic effect	2	0
Overall Study Withdrawal by Subject	2	6
Overall Study Death	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Canakinumab n=74 Participants 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.	Placebo n=73 Participants 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.	Total n=147 Participants Total of all reporting groups
Age Continuous	63.9 years STANDARD_DEVIATION 7.70 • n=5 Participants	63.6 years STANDARD_DEVIATION 7.92 • n=7 Participants	63.7 years STANDARD_DEVIATION 7.78 • n=5 Participants
Sex: Female, Male Female	28 Participants n=5 Participants	31 Participants n=7 Participants	59 Participants n=5 Participants
Sex: Female, Male Male	46 Participants n=5 Participants	42 Participants n=7 Participants	88 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 25 and Week 45

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

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.

Outcome measures

Measure	Canakinumab n=74 Participants 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.	Placebo n=73 Participants 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.
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Change from Baseline at Week 25	-0.027 Liters Standard Deviation 0.1725	-0.006 Liters Standard Deviation 0.2545
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Change from Baseline at Week 45	-0.044 Liters Standard Deviation 0.1542	-0.033 Liters Standard Deviation 0.2512

PRIMARY outcome

Timeframe: Baseline, Week 25 and Week 45

Population: Safety population

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.

Outcome measures

Measure	Canakinumab n=74 Participants 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.	Placebo n=73 Participants 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.
Change From Baseline in Forced Expiratory Volume in 1 Second Percent Predicted Change from Baseline at Week 25	-0.2 Percent of predicted Standard Deviation 6.42	0.3 Percent of predicted Standard Deviation 8.86
Change From Baseline in Forced Expiratory Volume in 1 Second Percent Predicted Change from Baseline at Week 45	-1.0 Percent of predicted Standard Deviation 5.35	-0.7 Percent of predicted Standard Deviation 8.49

PRIMARY outcome

Timeframe: Baseline, Week 25 and Week 45

Population: Safety population

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.

Outcome measures

Measure	Canakinumab n=74 Participants 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.	Placebo n=73 Participants 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.
Change From Baseline in Forced Vital Capacity (FVC) Change from Baseline at Week 25	-0.010 liters Standard Deviation 0.3720	-0.061 liters Standard Deviation 0.4856
Change From Baseline in Forced Vital Capacity (FVC) Change from Baseline at Week 45	-0.039 liters Standard Deviation 0.3122	-0.065 liters Standard Deviation 0.5170

PRIMARY outcome

Timeframe: Baseline, Week 25 and Week 45

Population: Safety population

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.

Outcome measures

Measure	Canakinumab n=74 Participants 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.	Placebo n=73 Participants 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.
Change From Baseline in Slow Vital Capacity (SVC) Change from Baseline at Week 25	-0.029 liters Standard Deviation 0.3746	-0.019 liters Standard Deviation 0.5082
Change From Baseline in Slow Vital Capacity (SVC) Change from Baseline at Week 45	-0.062 liters Standard Deviation 0.3727	-0.017 liters Standard Deviation 0.5379

PRIMARY outcome

Timeframe: Baseline, Week 25 and Week 45

Population: Safety population

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.

Outcome measures

Measure	Canakinumab n=74 Participants 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.	Placebo n=73 Participants 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.
Change From Baseline in Forced Expiratory Flow 25% to 75% Change from Baseline at Week 25	-0.022 L/sec Standard Deviation 0.1060	-0.002 L/sec Standard Deviation 0.1111
Change From Baseline in Forced Expiratory Flow 25% to 75% Change from Baseline at Week 45	-0.024 L/sec Standard Deviation 0.0898	-0.012 L/sec Standard Deviation 0.1244

SECONDARY outcome

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

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

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.

Outcome measures

Measure	Canakinumab n=74 Participants 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.	Placebo n=73 Participants 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.
Number of Participants Who Experienced Serious Adverse Events or Discontinued Due to Adverse Events Serious Adverse Events	23 Participants	14 Participants
Number of Participants Who Experienced Serious Adverse Events or Discontinued Due to Adverse Events Death	1 Participants	0 Participants
Number of Participants Who Experienced Serious Adverse Events or Discontinued Due to Adverse Events Discontinued due to Adverse Events	4 Participants	4 Participants
Number of Participants Who Experienced Serious Adverse Events or Discontinued Due to Adverse Events Discontinued due to Serious Adverse Events	3 Participants	4 Participants
Number of Participants Who Experienced Serious Adverse Events or Discontinued Due to Adverse Events Discontinued due to non-serious AEs	1 Participants	0 Participants

Adverse Events

Canakinumab

Serious events: 23 serious events

Other events: 59 other events

Deaths: 0 deaths

Placebo

Serious events: 14 serious events

Other events: 51 other events

Deaths: 0 deaths

Serious adverse events

Measure	Canakinumab n=74 participants at risk 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.	Placebo n=73 participants at risk 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.
Cardiac disorders Acute myocardial infarction	0.00% 0/74 • Adverse events were collected over the 45-week treatment period.	1.4% 1/73 • Adverse events were collected over the 45-week treatment period.
Cardiac disorders Angina unstable	0.00% 0/74 • Adverse events were collected over the 45-week treatment period.	1.4% 1/73 • Adverse events were collected over the 45-week treatment period.
Cardiac disorders Atrial fibrillation	1.4% 1/74 • Adverse events were collected over the 45-week treatment period.	0.00% 0/73 • Adverse events were collected over the 45-week treatment period.
Cardiac disorders Coronary artery disease	1.4% 1/74 • Adverse events were collected over the 45-week treatment period.	1.4% 1/73 • Adverse events were collected over the 45-week treatment period.
Cardiac disorders Palpitations	0.00% 0/74 • Adverse events were collected over the 45-week treatment period.	1.4% 1/73 • Adverse events were collected over the 45-week treatment period.
Cardiac disorders Supraventricular tachycardia	0.00% 0/74 • Adverse events were collected over the 45-week treatment period.	1.4% 1/73 • Adverse events were collected over the 45-week treatment period.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/74 • Adverse events were collected over the 45-week treatment period.	1.4% 1/73 • Adverse events were collected over the 45-week treatment period.
Gastrointestinal disorders Peptic ulcer	0.00% 0/74 • Adverse events were collected over the 45-week treatment period.	1.4% 1/73 • Adverse events were collected over the 45-week treatment period.
General disorders Chest discomfort	0.00% 0/74 • Adverse events were collected over the 45-week treatment period.	1.4% 1/73 • Adverse events were collected over the 45-week treatment period.
General disorders Chest pain	1.4% 1/74 • Adverse events were collected over the 45-week treatment period.	1.4% 1/73 • Adverse events were collected over the 45-week treatment period.
General disorders Oedema peripheral	0.00% 0/74 • Adverse events were collected over the 45-week treatment period.	1.4% 1/73 • Adverse events were collected over the 45-week treatment period.
Immune system disorders Oral allergy syndrome	0.00% 0/74 • Adverse events were collected over the 45-week treatment period.	1.4% 1/73 • Adverse events were collected over the 45-week treatment period.
Infections and infestations Bronchitis	2.7% 2/74 • Adverse events were collected over the 45-week treatment period.	0.00% 0/73 • Adverse events were collected over the 45-week treatment period.
Infections and infestations Bronchopulmonary aspergillosis	2.7% 2/74 • Adverse events were collected over the 45-week treatment period.	0.00% 0/73 • Adverse events were collected over the 45-week treatment period.
Infections and infestations Cellulitis	0.00% 0/74 • Adverse events were collected over the 45-week treatment period.	1.4% 1/73 • Adverse events were collected over the 45-week treatment period.
Infections and infestations Pneumonia	5.4% 4/74 • Adverse events were collected over the 45-week treatment period.	4.1% 3/73 • Adverse events were collected over the 45-week treatment period.
Infections and infestations Pneumonia mycoplasmal	1.4% 1/74 • Adverse events were collected over the 45-week treatment period.	0.00% 0/73 • Adverse events were collected over the 45-week treatment period.
Infections and infestations Sepsis	1.4% 1/74 • Adverse events were collected over the 45-week treatment period.	0.00% 0/73 • Adverse events were collected over the 45-week treatment period.
Infections and infestations Staphylococcal abscess	1.4% 1/74 • Adverse events were collected over the 45-week treatment period.	0.00% 0/73 • Adverse events were collected over the 45-week treatment period.
Infections and infestations Staphylococcal infection	2.7% 2/74 • Adverse events were collected over the 45-week treatment period.	0.00% 0/73 • Adverse events were collected over the 45-week treatment period.
Injury, poisoning and procedural complications Drug toxicity	1.4% 1/74 • Adverse events were collected over the 45-week treatment period.	0.00% 0/73 • Adverse events were collected over the 45-week treatment period.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chronic lymphocytic leukaemia	1.4% 1/74 • Adverse events were collected over the 45-week treatment period.	0.00% 0/73 • Adverse events were collected over the 45-week treatment period.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	1.4% 1/74 • Adverse events were collected over the 45-week treatment period.	0.00% 0/73 • Adverse events were collected over the 45-week treatment period.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Small cell lung cancer stage unspecified	1.4% 1/74 • Adverse events were collected over the 45-week treatment period.	0.00% 0/73 • Adverse events were collected over the 45-week treatment period.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ureteric cancer	1.4% 1/74 • Adverse events were collected over the 45-week treatment period.	0.00% 0/73 • Adverse events were collected over the 45-week treatment period.
Nervous system disorders Carotid artery stenosis	1.4% 1/74 • Adverse events were collected over the 45-week treatment period.	0.00% 0/73 • Adverse events were collected over the 45-week treatment period.
Reproductive system and breast disorders Benign prostatic hyperplasia	2.7% 2/74 • Adverse events were collected over the 45-week treatment period.	0.00% 0/73 • Adverse events were collected over the 45-week treatment period.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	1.4% 1/74 • Adverse events were collected over the 45-week treatment period.	1.4% 1/73 • Adverse events were collected over the 45-week treatment period.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	12.2% 9/74 • Adverse events were collected over the 45-week treatment period.	9.6% 7/73 • Adverse events were collected over the 45-week treatment period.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/74 • Adverse events were collected over the 45-week treatment period.	1.4% 1/73 • Adverse events were collected over the 45-week treatment period.
Respiratory, thoracic and mediastinal disorders Respiratory failure	1.4% 1/74 • Adverse events were collected over the 45-week treatment period.	0.00% 0/73 • Adverse events were collected over the 45-week treatment period.
Skin and subcutaneous tissue disorders Skin ulcer	1.4% 1/74 • Adverse events were collected over the 45-week treatment period.	0.00% 0/73 • Adverse events were collected over the 45-week treatment period.
Skin and subcutaneous tissue disorders Swelling face	0.00% 0/74 • Adverse events were collected over the 45-week treatment period.	1.4% 1/73 • Adverse events were collected over the 45-week treatment period.

Other adverse events

Measure	Canakinumab n=74 participants at risk 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.	Placebo n=73 participants at risk 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.
Gastrointestinal disorders Diarrhoea	6.8% 5/74 • Adverse events were collected over the 45-week treatment period.	6.8% 5/73 • Adverse events were collected over the 45-week treatment period.
Gastrointestinal disorders Dyspepsia	0.00% 0/74 • Adverse events were collected over the 45-week treatment period.	5.5% 4/73 • Adverse events were collected over the 45-week treatment period.
Gastrointestinal disorders Nausea	6.8% 5/74 • Adverse events were collected over the 45-week treatment period.	8.2% 6/73 • Adverse events were collected over the 45-week treatment period.
Gastrointestinal disorders Vomiting	6.8% 5/74 • Adverse events were collected over the 45-week treatment period.	1.4% 1/73 • Adverse events were collected over the 45-week treatment period.
General disorders Pyrexia	9.5% 7/74 • Adverse events were collected over the 45-week treatment period.	9.6% 7/73 • Adverse events were collected over the 45-week treatment period.
Infections and infestations Candidiasis	2.7% 2/74 • Adverse events were collected over the 45-week treatment period.	5.5% 4/73 • Adverse events were collected over the 45-week treatment period.
Infections and infestations Gastroenteritis viral	5.4% 4/74 • Adverse events were collected over the 45-week treatment period.	2.7% 2/73 • Adverse events were collected over the 45-week treatment period.
Infections and infestations Oral candidiasis	4.1% 3/74 • Adverse events were collected over the 45-week treatment period.	5.5% 4/73 • Adverse events were collected over the 45-week treatment period.
Infections and infestations Sinusitis	8.1% 6/74 • Adverse events were collected over the 45-week treatment period.	6.8% 5/73 • Adverse events were collected over the 45-week treatment period.
Infections and infestations Upper respiratory tract infection	12.2% 9/74 • Adverse events were collected over the 45-week treatment period.	5.5% 4/73 • Adverse events were collected over the 45-week treatment period.
Infections and infestations Urinary tract infection	5.4% 4/74 • Adverse events were collected over the 45-week treatment period.	5.5% 4/73 • Adverse events were collected over the 45-week treatment period.
Musculoskeletal and connective tissue disorders Back pain	6.8% 5/74 • Adverse events were collected over the 45-week treatment period.	5.5% 4/73 • Adverse events were collected over the 45-week treatment period.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	51.4% 38/74 • Adverse events were collected over the 45-week treatment period.	49.3% 36/73 • Adverse events were collected over the 45-week treatment period.
Respiratory, thoracic and mediastinal disorders Cough	10.8% 8/74 • Adverse events were collected over the 45-week treatment period.	8.2% 6/73 • Adverse events were collected over the 45-week treatment period.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.4% 1/74 • Adverse events were collected over the 45-week treatment period.	5.5% 4/73 • Adverse events were collected over the 45-week treatment period.
Vascular disorders Hypertension	5.4% 4/74 • Adverse events were collected over the 45-week treatment period.	1.4% 1/73 • Adverse events were collected over the 45-week treatment period.

Additional Information

Novartis Pharmaceuticals

Study Director

Phone: 862-778-8300

Results disclosure agreements

• Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
• Publication restrictions are in place

Restriction type: OTHER