- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00670007
Extension Study of Zemaira® i.v. Administration in Subjects With Emphysema Due to alpha1-proteinase Inhibitor Deficiency.
July 13, 2016 updated by: CSL Behring
An Open-label, Non-controlled, Multicenter, Multinational Study to Evaluate the Efficacy and Safety of Zemaira® Administration in Chronic Augmentation and Maintenance Therapy in Subjects With Emphysema Due to alpha1-proteinase Inhibitor Deficiency Who Completed Clinical Study CE1226_4001
This study is a continuation of the placebo-controlled study CE1226_4001 (NCT00261833) to evaluate the efficacy and safety of Zemaira® intravenous (i.v).
administration in subjects with emphysema due to alpha1-proteinase inhibitor deficiency.
The long-term verification of a disease-modifying benefit of Zemaira® on the progression of emphysema will be assessed by volume-adjusted lung density, measured yearly by computed tomography (CT).
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
140
Phase
- Phase 4
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Darlinghurst, Australia, 2010
- Study site
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Nedlands, Australia, 6009
- Study site
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New Lambton, Australia, 2305
- Study site
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South Australia
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Adelaide, South Australia, Australia, 5000
- Study site
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Victoria
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Fitzroy, Victoria, Australia, 3065
- Study site
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British Columbia
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Vancouver, British Columbia, Canada, V6J1S3
- Study site
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Nova Scotia
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Halifax, Nova Scotia, Canada, B3H 3A7
- Study site
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Ontario
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Toronto, Ontario, Canada, M5T 2S8
- Study site
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Praha 4 - Krc, Czech Republic, 14059
- Study site
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Arhus C, Denmark, 8000
- Study site
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Hellerup, Denmark, 2900
- Study site
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Tartu, Estonia, 51014
- Study site
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Oulu, Finland, 90220
- Study site
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Essen, Germany, 45239
- Study site
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Heidelberg, Germany, 69126
- Study site
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Nürnberg, Germany, 90419
- Study site
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Dublin, Ireland, 9
- Study site
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Krakow, Poland, 31-066
- Study site
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Warsaw, Poland, 01-138
- Study site
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Bucuresti, Romania, 011026
- Study site
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Malmo, Sweden, 20502
- Study site
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Subjects who have completed the 2-year treatment and observation period in the Phase 3/4 Zemaira® CE1226_4001 study (NCT00261833) and are willing to sign informed consent
- Males, and non-pregnant, non-lactating females, whose screening pregnancy test is negative and who are using contraceptive methods deemed reliable by the investigator
Exclusion Criteria:
- Individuals residing in the US
- Current evidence of alcohol abuse or abuse of drugs such as barbiturates, benzodiazepines, amphetamines, cocaine, opioids, and cannabinoids
- History of allergy, anaphylactic reaction, or severe systemic response to human plasma derived products, or known mannitol hypersensitivity, or history of prior adverse reaction to mannitol
- Current tobacco smoker (smoking must be discontinued for at least 6 months prior to study participation)
- Conditions or behaviors that interfere with attending scheduled study visits in the opinion of the investigator
- History of non-compliance
- Administration of any other experimental new drug or participation in an investigation of a marketed product
- Inability to perform necessary study procedures
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Zemaira®
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Lyophilized preparation of 60 mg/kg body weight intravenously once per week
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Rate of Change of Adjusted Lung Density
Time Frame: Up to 2 years
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As measured by centralized, standardized computer tomographic (CT) lung densitometry.
CT scans were acquired at 2 inspiration states: TLC (Total Lung Capacity; ie, full inspiration) and FRC (Functional Residual Capacity; ie, full expiration).
Results were adjusted for total lung volume and are presented as point estimates for the average rate of decline in the early start and delayed start subgroups from a linear random regression model with country, inspiration state (only for 'TLC and FRC state'), time (time elapsed since Day 1 [CE1226_4001]), treatment and treatment by time interaction as fixed effects and subject and subject by time interaction as random coefficients.
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Up to 2 years
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Absolute Change in Adjusted Lung Density
Time Frame: From baseline to 2 years
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Absolute change from baseline to 2 years as measured by centralized, standardized CT lung densitometry.
CT scans were acquired at 2 inspiration states: TLC (ie, full inspiration) and FRC (ie, full expiration).
Results were adjusted for total lung volume and are presented as point estimates for the average absolute change in the early start and delayed start subgroups from an analysis of covariance (ANCOVA) model with country, treatment, and baseline lung density as fixed effects and inspiration state as a repeated random effect.
The baseline is the last assessment from the preceding study CE1226_4001.
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From baseline to 2 years
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Percent Change in Adjusted Lung Density
Time Frame: From baseline to 2 years
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Percent change from baseline to 2 years as measured by centralized, standardized CT lung densitometry.
CT scans were acquired at 2 inspiration states: TLC (ie, full inspiration) and FRC (ie, full expiration).
Results were adjusted for total lung volume and are presented as point estimates for the average percent change in the early start and delayed start subgroups from an analysis of covariance (ANCOVA) model with country, treatment, and baseline lung density as fixed effects and inspiration state as a repeated random effect.
The baseline is the last assessment from the preceding study CE1226_4001.
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From baseline to 2 years
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Change in Subject-reported Symptoms
Time Frame: From baseline to 2 years
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Patient-reported symptoms were measured using the St George's Respiratory Questionnaire (SGRQ).
SGRQ total, symptoms, activity and impact scores range from 0 to 100, with higher scores indicating more limitations, and change from baseline below zero (0) is favorable, indicating improvement.
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From baseline to 2 years
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Percent Change in Lung Function as Measured by Forced Expiratory Volume in 1 Second (FEV1)
Time Frame: From baseline up to 2 years
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From baseline up to 2 years
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Percent Change in Lung Function as Measured by Ratio of FEV1/FVC (Forced Vital Capacity)
Time Frame: From baseline up to 2 years
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From baseline up to 2 years
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Percent Change in Lung Function as Measured by Percent Predicted FEV1
Time Frame: From baseline up to 2 years
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From baseline up to 2 years
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Number of Subjects With Pulmonary Exacerbations
Time Frame: Up to 2 years
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Up to 2 years
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Annual Rate in Subject Years of Pulmonary Exacerbations
Time Frame: Up to 2 years
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Annual exposure-adjusted incidence rate of pulmonary exacerbations.
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Up to 2 years
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Time to First Pulmonary Exacerbation
Time Frame: Up to 2 years
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Up to 2 years
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Percentage of Subjects With Treatment Emergent Adverse Events
Time Frame: From baseline up to 2.5 years
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Percentage of subjects with treatment-emergent adverse events (TEAEs): overall, by severity, by relatedness, by seriousness, and which occurred within 24 hours of Zemaira administration.
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From baseline up to 2.5 years
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Greulich T, Chlumsky J, Wencker M, Vit O, Fries M, Chung T, Shebl A, Vogelmeier C, Chapman KR, McElvaney NG; RAPID Trial Group. Safety of biweekly alpha1-antitrypsin treatment in the RAPID programme. Eur Respir J. 2018 Nov 29;52(5):1800897. doi: 10.1183/13993003.00897-2018. Print 2018 Nov.
- McElvaney NG, Burdon J, Holmes M, Glanville A, Wark PA, Thompson PJ, Hernandez P, Chlumsky J, Teschler H, Ficker JH, Seersholm N, Altraja A, Makitaro R, Chorostowska-Wynimko J, Sanak M, Stoicescu PI, Piitulainen E, Vit O, Wencker M, Tortorici MA, Fries M, Edelman JM, Chapman KR; RAPID Extension Trial Group. Long-term efficacy and safety of alpha1 proteinase inhibitor treatment for emphysema caused by severe alpha1 antitrypsin deficiency: an open-label extension trial (RAPID-OLE). Lancet Respir Med. 2017 Jan;5(1):51-60. doi: 10.1016/S2213-2600(16)30430-1. Epub 2016 Dec 2. Erratum In: Lancet Respir Med. 2017 Feb;5(2):e13.
- Chapman KR, Burdon JG, Piitulainen E, Sandhaus RA, Seersholm N, Stocks JM, Stoel BC, Huang L, Yao Z, Edelman JM, McElvaney NG; RAPID Trial Study Group. Intravenous augmentation treatment and lung density in severe alpha1 antitrypsin deficiency (RAPID): a randomised, double-blind, placebo-controlled trial. Lancet. 2015 Jul 25;386(9991):360-8. doi: 10.1016/S0140-6736(15)60860-1. Epub 2015 May 27.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
April 1, 2008
Primary Completion (Actual)
September 1, 2014
Study Completion (Actual)
September 1, 2014
Study Registration Dates
First Submitted
April 29, 2008
First Submitted That Met QC Criteria
April 30, 2008
First Posted (Estimate)
May 1, 2008
Study Record Updates
Last Update Posted (Estimate)
August 15, 2016
Last Update Submitted That Met QC Criteria
July 13, 2016
Last Verified
July 1, 2016
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- Pathologic Processes
- Respiratory Tract Diseases
- Lung Diseases
- Liver Diseases
- Genetic Diseases, Inborn
- Lung Diseases, Obstructive
- Pulmonary Disease, Chronic Obstructive
- Subcutaneous Emphysema
- Pulmonary Emphysema
- Emphysema
- Alpha 1-Antitrypsin Deficiency
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Serine Proteinase Inhibitors
- Trypsin Inhibitors
- Protease Inhibitors
- Alpha 1-Antitrypsin
Other Study ID Numbers
- CE1226_3001
- 1466 (CSL Behring)
- 2007-007129-38 (EudraCT Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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