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

Status

Completed

Phases

Phase 1Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00581945

Enrollment

147

Registered

2007-12-28

Start date

2007-01-31

Completion date

2010-05-31

Last updated

2011-06-30

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Chronic Obstructive Pulmonary Disease

Brief 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

Interventions

DRUGCanakinumab

The dose of canakinumab (ACZ885) administered was individualized, based on the subject's weight pre-dose, and was administered via intravenous infusion.

DRUGPlacebo

Matching placebo to ACZ885 administered via intravenous infusion.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

BASIC_SCIENCE

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

40 Years to 80 Years

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)	Baseline, Week 25 and Week 45	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	Baseline, Week 25 and Week 45	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)	Baseline, Week 25 and Week 45	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)	Baseline, Week 25 and Week 45	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%	Baseline, Week 25 and Week 45	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

Measure	Time frame	Description
Number of Participants Who Experienced Serious Adverse Events or Discontinued Due to Adverse Events	Adverse events were collected during the 45 week treatment period and the 12 week follow-up period.	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.

Countries

United States

Participant flow

Participants by arm

Arm	Count
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.	74
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.	73
Total	147

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	4	4
Overall Study	Death	1	0
Overall Study	Unsatisfactory therapeutic effect	2	0
Overall Study	Withdrawal by Subject	2	6

Baseline characteristics

Characteristic	Canakinumab	Placebo	Total
Age Continuous	63.9 years STANDARD_DEVIATION 7.7	63.6 years STANDARD_DEVIATION 7.92	63.7 years STANDARD_DEVIATION 7.78
Sex: Female, Male Female	28 Participants	31 Participants	59 Participants
Sex: Female, Male Male	46 Participants	42 Participants	88 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	59 / 74	51 / 73
serious Total, serious adverse events	23 / 74	14 / 73

Outcome results

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.