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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
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
Secondary ID [1] 0 0
1449
Secondary ID [2] 0 0
CE1226_4001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alpha1-proteinase Inhibitor Deficiency 0 0
Emphysema 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Respiratory 0 0 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
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
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Annual Rate of Change in Lung Density
Timepoint [1] 0 0
Over a 2-year period
Secondary outcome [1] 0 0
Annual Rate of Pulmonary Exacerbations
Timepoint [1] 0 0
Over a 2-year period
Secondary outcome [2] 0 0
Percent Change in FEV1
Timepoint [2] 0 0
From baseline to 2 years
Secondary outcome [3] 0 0
Time to First Pulmonary Exacerbation
Timepoint [3] 0 0
Over a 2-year period
Secondary outcome [4] 0 0
Change in Lung Density
Timepoint [4] 0 0
From baseline to 2 years
Secondary outcome [5] 0 0
Change in Exercise Capacity
Timepoint [5] 0 0
From baseline to 2 years
Secondary outcome [6] 0 0
Change in Patient-reported Symptoms
Timepoint [6] 0 0
From baseline to 2 years
Secondary outcome [7] 0 0
Frequency and Intensity of Adverse Events (AEs)
Timepoint [7] 0 0
Over a 2-year period
Secondary outcome [8] 0 0
Percent Change in Percent Predicted FEV1
Timepoint [8] 0 0
From baseline to 2 years
Secondary outcome [9] 0 0
Percent Change in FEV1 Divided by Forced Vital Capacity
Timepoint [9] 0 0
From baseline to 2 years
Secondary outcome [10] 0 0
Percent Change in DLCO
Timepoint [10] 0 0
From baseline to 2 years
Secondary outcome [11] 0 0
Duration of Pulmonary Exacerbations Relative to Treatment Duration
Timepoint [11] 0 0
Over a 2-year period
Secondary outcome [12] 0 0
Severity of Pulmonary Exacerbations
Timepoint [12] 0 0
Over a 2-year period

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.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
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
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/03/2006
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/09/2012
Sample size
Target
Accrual to date
Final
180
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,WA
Recruitment hospital [1] 0 0
Study Site - Darlinghurst
Recruitment hospital [2] 0 0
Study Site - New Lambton
Recruitment hospital [3] 0 0
Study Site - Brisbane
Recruitment hospital [4] 0 0
Study Site - Adelaide
Recruitment hospital [5] 0 0
Study Site - Nedlands
Recruitment hospital [6] 0 0
Study Site - Fitzroy
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
2305 - New Lambton
Recruitment postcode(s) [3] 0 0
4066 - Brisbane
Recruitment postcode(s) [4] 0 0
5000 - Adelaide
Recruitment postcode(s) [5] 0 0
6009 - Nedlands
Recruitment postcode(s) [6] 0 0
3065 - Fitzroy
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Colorado
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Pennsylvania
Country [4] 0 0
United States of America
State/province [4] 0 0
Texas
Country [5] 0 0
Canada
State/province [5] 0 0
British Columbia
Country [6] 0 0
Canada
State/province [6] 0 0
Nova Scotia
Country [7] 0 0
Canada
State/province [7] 0 0
Ontario
Country [8] 0 0
Czech Republic
State/province [8] 0 0
Praha
Country [9] 0 0
Denmark
State/province [9] 0 0
Arhus
Country [10] 0 0
Denmark
State/province [10] 0 0
Hellerup
Country [11] 0 0
Estonia
State/province [11] 0 0
Tartu
Country [12] 0 0
Finland
State/province [12] 0 0
Oulu
Country [13] 0 0
Germany
State/province [13] 0 0
Berlin
Country [14] 0 0
Germany
State/province [14] 0 0
Essen
Country [15] 0 0
Germany
State/province [15] 0 0
Heidelberg
Country [16] 0 0
Germany
State/province [16] 0 0
Nürnberg
Country [17] 0 0
Ireland
State/province [17] 0 0
Dublin
Country [18] 0 0
Poland
State/province [18] 0 0
Krakow
Country [19] 0 0
Poland
State/province [19] 0 0
Warsaw
Country [20] 0 0
Romania
State/province [20] 0 0
Bucuresti
Country [21] 0 0
Russian Federation
State/province [21] 0 0
Barnaul
Country [22] 0 0
Sweden
State/province [22] 0 0
Malmo

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
CSL Behring
Address
Country

Ethics approval
Ethics application status

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).
Trial website
https://clinicaltrials.gov/study/NCT00261833
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.
Public notes

Contacts
Principal investigator
Name 0 0
Senior Director Immonology & Pulmonology, Clinical R&D
Address 0 0
CSL Behring
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00261833