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

Primary Purpose

Chronic Obstructive Pulmonary Disease

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Canakinumab
Placebo
Sponsored by
Novartis
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Chronic Obstructive Pulmonary Disease

Eligibility Criteria

40 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Canakinumab

Placebo

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.
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.
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.
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.
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 Outcome Measures

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.

Full Information

First Posted
December 21, 2007
Last Updated
June 28, 2011
Sponsor
Novartis
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1. Study Identification

Unique Protocol Identification Number
NCT00581945
Brief Title
Safety and Efficacy of Multiple Doses of Canakinumab (ACZ885) in Chronic Obstructive Pulmonary Disease (COPD) Patients
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2011
Overall Recruitment Status
Completed
Study Start Date
January 2007 (undefined)
Primary Completion Date
May 2010 (Actual)
Study Completion Date
May 2010 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Novartis

4. Oversight

Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Obstructive Pulmonary Disease

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
147 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Canakinumab
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Canakinumab
Intervention Description
The dose of canakinumab (ACZ885) administered was individualized, based on the subject's weight pre-dose, and was administered via intravenous infusion.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching placebo to ACZ885 administered via intravenous infusion.
Primary Outcome Measure Information:
Title
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)
Description
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.
Time Frame
Baseline, Week 25 and Week 45
Title
Change From Baseline in Forced Expiratory Volume in 1 Second Percent Predicted
Description
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.
Time Frame
Baseline, Week 25 and Week 45
Title
Change From Baseline in Forced Vital Capacity (FVC)
Description
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.
Time Frame
Baseline, Week 25 and Week 45
Title
Change From Baseline in Slow Vital Capacity (SVC)
Description
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.
Time Frame
Baseline, Week 25 and Week 45
Title
Change From Baseline in Forced Expiratory Flow 25% to 75%
Description
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.
Time Frame
Baseline, Week 25 and Week 45
Secondary Outcome Measure Information:
Title
Number of Participants Who Experienced Serious Adverse Events or Discontinued Due to Adverse Events
Description
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.
Time Frame
Adverse events were collected during the 45 week treatment period and the 12 week follow-up period.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
NOVARTIS
Organizational Affiliation
Novartis investigator site
Official's Role
Principal Investigator
Facility Information:
Facility Name
Novartis Investigator Site
City
Anaheim
State/Province
California
ZIP/Postal Code
92801
Country
United States
Facility Name
Novartis Investigator Site
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Novartis Investigator Site
City
Panama City
State/Province
Florida
ZIP/Postal Code
32405
Country
United States
Facility Name
Novartis Investigator Site
City
Marietta
State/Province
Georgia
ZIP/Postal Code
300060
Country
United States
Facility Name
Novartis Investigator Site
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21224
Country
United States
Facility Name
Novartis Investigator Site
City
Livonia
State/Province
Michigan
ZIP/Postal Code
48152
Country
United States
Facility Name
Novartis Investigator Site
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55402
Country
United States
Facility Name
Novartis Investigator Site
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198-5885
Country
United States
Facility Name
Novartis Investigator Site
City
Buffalo
State/Province
New York
ZIP/Postal Code
14215
Country
United States
Facility Name
Novartis Investigator Site
City
Spartanburg
State/Province
South Carolina
ZIP/Postal Code
29303
Country
United States
Facility Name
Novartis Investigator Site
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23225
Country
United States

12. IPD Sharing Statement

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

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