- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00261833
Zemaira in Subjects With Emphysema Due to Alpha1-Proteinase Inhibitor Deficiency
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
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
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Fitzroy, Australia, 3065
- Study Site
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New South Wales
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Darlinghurst, New South Wales, Australia, 2010
- Study Site
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New Lambton, New South Wales, Australia, 2305
- Study Site
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Queensland
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Brisbane, Queensland, Australia, 4066
- Study Site
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South Australia
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Adelaide, South Australia, Australia, 5000
- Study Site
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Western Australia
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Nedlands, Western Australia, Australia, 6009
- Study Site
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British Columbia
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Vancouver, British Columbia, Canada, V5Z4E1
- Study Site
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Nova Scotia
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Halifax, Nova Scotia, Canada, B3H3A7
- Study Site
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Ontario
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Toronto, Ontario, Canada, M5T2S8
- Study Site
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Praha, Czech Republic, 14059
- Study Site
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Arhus, 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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Berlin, Germany, 12200
- 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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Barnaul, Russian Federation
- Study Site
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Malmo, Sweden, 20502
- Study Site
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Colorado
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Denver, Colorado, United States, 80206
- Study Site
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Florida
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Miami, Florida, United States, 33136
- Study Site
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Pennsylvania
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Hershey, Pennsylvania, United States, 17033
- Study Site
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Texas
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Tyler, Texas, United States, 75708
- Study Site
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
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 Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Placebo Comparator: Placebo
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Lyophilized preparation: 60 mg/kg body weight/week intravenous
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Experimental: Zemaira®
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60 mg/kg body weight/week intravenous
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Annual Rate of Change in Lung Density
Time Frame: Over a 2-year period
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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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Over a 2-year period
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Annual Rate of Pulmonary Exacerbations
Time Frame: Over a 2-year period
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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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Over a 2-year period
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Percent Change in FEV1
Time Frame: From baseline to 2 years
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Percent change from baseline to Month 24.
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From baseline to 2 years
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Time to First Pulmonary Exacerbation
Time Frame: Over a 2-year period
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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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Over a 2-year period
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Change in Lung Density
Time Frame: From baseline to 2 years
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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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From baseline to 2 years
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Change in Exercise Capacity
Time Frame: From baseline to 2 years
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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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From baseline to 2 years
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Change in Patient-reported Symptoms
Time Frame: From baseline to 2 years
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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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From baseline to 2 years
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Frequency and Intensity of Adverse Events (AEs)
Time Frame: Over a 2-year period
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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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Over a 2-year period
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Percent Change in Percent Predicted FEV1
Time Frame: From baseline to 2 years
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Percent change from baseline to Month 24.
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From baseline to 2 years
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Percent Change in FEV1 Divided by Forced Vital Capacity
Time Frame: From baseline to 2 years
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Percent change from baseline to Month 24.
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From baseline to 2 years
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Percent Change in DLCO
Time Frame: From baseline to 2 years
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Percent change from baseline to Month 24.
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From baseline to 2 years
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Duration of Pulmonary Exacerbations Relative to Treatment Duration
Time Frame: Over a 2-year period
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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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Over a 2-year period
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Severity of Pulmonary Exacerbations
Time Frame: Over a 2-year period
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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. |
Over a 2-year period
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Other Outcome Measures
Outcome Measure |
Time Frame |
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Baseline Lung Density at Total Lung Capacity (TLC) and Forced Residual Capacity (FRC)
Time Frame: Baseline
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Baseline
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Collaborators and Investigators
Sponsor
Investigators
- Study Director: Senior Director Immonology & Pulmonology, Clinical R&D, CSL Behring
Publications and helpful links
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.
- 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
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
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_4001
- 1449 (Other Identifier: CSL Behring)
- 2005-003459-12 (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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