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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT00261833
Registration number
NCT00261833
Ethics application status
Date submitted
2/12/2005
Date registered
5/12/2005
Date last updated
19/01/2015
Titles & IDs
Public title
Zemaira in Subjects With Emphysema Due to Alpha1-Proteinase Inhibitor Deficiency
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Scientific title
A Randomized, Placebo-Controlled, Double-Blind, Multicenter Phase III/IV Study to Compare the Efficacy and Safety of 60mg/kg Body Weight of Zemaira® Weekly I.V. Administration With Placebo Weekly I.V. Administration in Chronic Augmentation and Maintenance Therapy in Subjects With Emphysema Due to Alpha1-Proteinase Inhibitor Deficiency
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Secondary ID [1]
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1449
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Secondary ID [2]
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CE1226_4001
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Alpha1-proteinase Inhibitor Deficiency
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Emphysema
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Condition category
Condition code
Human Genetics and Inherited Disorders
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Other human genetics and inherited disorders
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Respiratory
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Other respiratory disorders / diseases
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Other - Alpha1-proteinase inhibitor
Other interventions - Placebo
Experimental: Zemaira® -
Placebo comparator: Placebo -
Treatment: Other: Alpha1-proteinase inhibitor
60 mg/kg body weight/week intravenous
Other interventions: Placebo
Lyophilized preparation: 60 mg/kg body weight/week intravenous
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Intervention code [1]
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Treatment: Other
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Intervention code [2]
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Other interventions
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Annual Rate of Change in Lung Density
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Assessment method [1]
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As measured by centralized, standardized computer tomographic (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 rate of decline in each treatment group.
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Timepoint [1]
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Over a 2-year period
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Secondary outcome [1]
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Annual Rate of Pulmonary Exacerbations
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Assessment method [1]
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Primary diagnostic criteria for exacerbations were increased dyspnea, increased sputum volume, and increased sputum purulence. Supporting diagnostic criteria were upper respiratory tract infection, fever without other apparent cause, increased wheezing, and increased cough. For diagnosis, participants had to meet 2 of the 3 primary criteria or 1 primary criterion and 1 supporting criterion. The annual rate was based on the total number of exacerbations and the total number of participant study days for all participants in the specified analysis population and adjusted to 365.25 days.
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Timepoint [1]
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Over a 2-year period
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Secondary outcome [2]
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Percent Change in FEV1
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Assessment method [2]
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Percent change from baseline to Month 24.
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Timepoint [2]
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From baseline to 2 years
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Secondary outcome [3]
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Time to First Pulmonary Exacerbation
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Assessment method [3]
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Primary diagnostic criteria for exacerbations were increased dyspnea, increased sputum volume, and increased sputum purulence. Supporting diagnostic criteria were upper respiratory tract infection, fever without other apparent cause, increased wheezing, and increased cough. For diagnosis, participants had to meet 2 of the 3 primary criteria or 1 primary criterion and 1 supporting criterion.
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Timepoint [3]
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Over a 2-year period
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Secondary outcome [4]
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Change in Lung Density
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Assessment method [4]
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Change from baseline to Month 24 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.
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Timepoint [4]
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From baseline to 2 years
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Secondary outcome [5]
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Change in Exercise Capacity
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Assessment method [5]
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Exercise capacity was measured as distance walked, using the incremental shuttle walk test. Change from baseline to end of treatment (2 years) in exercise capacity was analysed using an analysis of covariance (ANCOVA).
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Timepoint [5]
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From baseline to 2 years
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Secondary outcome [6]
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Change in Patient-reported Symptoms
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Assessment method [6]
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Patient-reported symptoms were measured using the symptoms score component of the St George's Respiratory Questionnaire (SGRQ). SGRQ scores range from 0 to 100, with higher scores indicating more limitations and negative values for change indicating improvement. Change from baseline to end of treatment (2 years) in SGRQ was analysed using an ANCOVA.
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Timepoint [6]
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From baseline to 2 years
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Secondary outcome [7]
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Frequency and Intensity of Adverse Events (AEs)
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Assessment method [7]
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Number of participants with at least one AE, and the number of participants with mild, moderate or severe AEs. AE intensity was defined as mild (does not interfere with routine activities), moderate (interferes with routine activities), or severe (impossible to perform routine activities).
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Timepoint [7]
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Over a 2-year period
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Secondary outcome [8]
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Percent Change in Percent Predicted FEV1
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Assessment method [8]
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Percent change from baseline to Month 24.
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Timepoint [8]
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From baseline to 2 years
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Secondary outcome [9]
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Percent Change in FEV1 Divided by Forced Vital Capacity
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Assessment method [9]
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Percent change from baseline to Month 24.
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Timepoint [9]
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From baseline to 2 years
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Secondary outcome [10]
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Percent Change in DLCO
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Assessment method [10]
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Percent change from baseline to Month 24.
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Timepoint [10]
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From baseline to 2 years
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Secondary outcome [11]
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Duration of Pulmonary Exacerbations Relative to Treatment Duration
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Assessment method [11]
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Defined as the percentage of total treatment duration across participants for 1) exacerbations overall, 2) antibiotic treatment for exacerbations, and 3) hospitalization for exacerbations. Primary diagnostic criteria for exacerbations were increased dyspnea, increased sputum volume, and increased sputum purulence. Supporting diagnostic criteria were upper respiratory tract infection, fever without other apparent cause, increased wheezing, and increased cough. For diagnosis, participants had to meet 2 of the 3 primary criteria or 1 primary criterion and 1 supporting criterion.
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Timepoint [11]
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Over a 2-year period
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Secondary outcome [12]
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Severity of Pulmonary Exacerbations
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Assessment method [12]
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Defined as the number of participants requiring 1) antibiotic treatment for exacerbations, and 2) hospitalization for exacerbations. Primary diagnostic criteria for exacerbations were increased dyspnea, increased sputum volume, and increased sputum purulence. Supporting diagnostic criteria were upper respiratory tract infection, fever without other apparent cause, increased wheezing, and increased cough. For diagnosis, participants had to meet 2 of the 3 primary criteria or 1 primary criterion and 1 supporting criterion.
Antibiotic treatment usage was reported by quarterly interval.
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Timepoint [12]
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Over a 2-year period
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Eligibility
Key inclusion criteria
* 18 to 65 years of age and willing to sign informed consent.
* Males and non-pregnant, non-lactating females whose screening pregnancy test is negative and who are using contraceptives methods deemed reliable by the investigator.
* Diagnosis of alpha1-proteinase inhibitor (A1-PI) deficiency (serum A1-PI levels < 11 µM or < 80 mg/dL). This includes newly diagnosed subjects, previously untreated subjects, currently treated subjects, and subjects currently not on treatment therapy but on treatment in the past.
* Subjects with emphysema and forced expiratory volume in 1 second (FEV1) = 35% and = 70% (predicted).
* No signs of chronic or acute Hepatitis A, Hepatitis B, Hepatitis C or HIV infection (negative serologies for HIV and viral hepatitis). In case of positive serologies for viral hepatitis, vaccination status or negative IgM should be available.
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Minimum age
18
Years
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Maximum age
65
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
* Any relevant chronic diseases or history of relevant diseases (e.g., severe renal insufficiency) except respiratory or liver disease secondary to alpha1-proteinase inhibitor deficiency. Subjects with well-controlled, chronic diseases may be included after consultation with the treating physician and the sponsor.
* Current evidence of alcohol abuse or history of abuse of illegal and/or legally prescribed 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.
* History of transfusion reactions.
* Selective IgA deficiency.
* Acute illness within one week prior to the first administration of the investigational medicinal product (IMP). Start of treatment after recovery is possible.
* Current tobacco smoker (smoking has to be ceased at least 6 months prior study inclusion). Subjects with a positive cotinine test due to nicotine replacement therapy (e.g. patches, chewing gum) or snuff are eligible.
* 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 within one month prior to the screening visit date.
* Inability to perform necessary study procedures.
* Lung transplantation, lung volume reduction surgery or lobectomy or being on a waiting list for any such surgeries.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Blinded (masking used)
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Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 4
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
1/03/2006
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
1/09/2012
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Sample size
Target
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Accrual to date
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Final
180
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Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,WA
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Recruitment hospital [1]
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Study Site - Darlinghurst
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Recruitment hospital [2]
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Study Site - New Lambton
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Recruitment hospital [3]
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Study Site - Brisbane
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Recruitment hospital [4]
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Study Site - Adelaide
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Recruitment hospital [5]
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Study Site - Nedlands
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Recruitment hospital [6]
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Study Site - Fitzroy
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Recruitment postcode(s) [1]
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2010 - Darlinghurst
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Recruitment postcode(s) [2]
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2305 - New Lambton
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Recruitment postcode(s) [3]
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4066 - Brisbane
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Recruitment postcode(s) [4]
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5000 - Adelaide
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Recruitment postcode(s) [5]
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6009 - Nedlands
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Recruitment postcode(s) [6]
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3065 - Fitzroy
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Recruitment outside Australia
Country [1]
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United States of America
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State/province [1]
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Colorado
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United States of America
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State/province [2]
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Florida
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United States of America
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State/province [3]
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Pennsylvania
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Country [4]
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United States of America
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State/province [4]
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Texas
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Country [5]
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Canada
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State/province [5]
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British Columbia
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Country [6]
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Canada
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State/province [6]
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Nova Scotia
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Country [7]
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Canada
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State/province [7]
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Ontario
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Country [8]
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Czech Republic
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State/province [8]
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Praha
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Denmark
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State/province [9]
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Arhus
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Denmark
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Hellerup
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Estonia
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State/province [11]
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Tartu
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Finland
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Oulu
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Germany
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Berlin
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Germany
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State/province [14]
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Essen
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Germany
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Heidelberg
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Germany
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State/province [16]
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Nürnberg
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Ireland
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State/province [17]
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Dublin
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Poland
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Krakow
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Poland
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State/province [19]
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Warsaw
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Country [20]
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Romania
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Bucuresti
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Russian Federation
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Barnaul
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Sweden
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State/province [22]
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Malmo
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
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Name
CSL Behring
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Address
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Country
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Ethics approval
Ethics application status
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Summary
Brief summary
This is a randomized, placebo-controlled, double-blind, multicenter phase III/IV study to compare the efficacy and safety of Zemaira® with placebo in subjects with emphysema due to alpha1-proteinase inhibitor deficiency. The effect of Zemaira® on the progression of emphysema will be assessed by the decline of lung density, measured by computed tomography (CT).
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Trial website
https://clinicaltrials.gov/study/NCT00261833
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Trial related presentations / 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. 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.
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Public notes
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Contacts
Principal investigator
Name
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Senior Director Immonology & Pulmonology, Clinical R&D
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Address
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CSL Behring
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Address
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Phone
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Fax
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Contact person for scientific queries
No information has been provided regarding IPD availability
What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results are available at
https://clinicaltrials.gov/study/NCT00261833
Download to PDF