Zemaira in Subjects With Emphysema Due to Alpha1-Proteinase Inhibitor Deficiency
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT00261833 |
|
Recruitment Status :
Completed
First Posted : December 5, 2005
Results First Posted : January 19, 2015
Last Update Posted : January 19, 2015
|
Sponsor:
CSL Behring
Information provided by (Responsible Party):
CSL Behring
- Study Details
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
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).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Alpha1-proteinase Inhibitor Deficiency Emphysema | Biological: Alpha1-proteinase inhibitor Other: Placebo | Phase 4 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 180 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official 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 |
| Study Start Date : | March 2006 |
| Actual Primary Completion Date : | September 2012 |
| Actual Study Completion Date : | September 2012 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Alpha-1 antitrypsin deficiency
| Arm | Intervention/treatment |
|---|---|
| Experimental: Zemaira® |
Biological: Alpha1-proteinase inhibitor
60 mg/kg body weight/week intravenous
Other Name: Zemaira® |
| Placebo Comparator: Placebo |
Other: Placebo
Lyophilized preparation: 60 mg/kg body weight/week intravenous |
Primary Outcome Measures :
- Annual Rate of Change in Lung Density [ Time Frame: Over a 2-year period ]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.
Secondary Outcome Measures :
- Annual Rate of Pulmonary Exacerbations [ Time Frame: Over a 2-year period ]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.
- Percent Change in FEV1 [ Time Frame: From baseline to 2 years ]Percent change from baseline to Month 24.
- Time to First Pulmonary Exacerbation [ Time Frame: Over a 2-year period ]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.
- Change in Lung Density [ Time Frame: From baseline to 2 years ]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.
- Change in Exercise Capacity [ Time Frame: From baseline to 2 years ]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).
- Change in Patient-reported Symptoms [ Time Frame: From baseline to 2 years ]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.
- Frequency and Intensity of Adverse Events (AEs) [ Time Frame: Over a 2-year period ]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).
- Percent Change in Percent Predicted FEV1 [ Time Frame: From baseline to 2 years ]Percent change from baseline to Month 24.
- Percent Change in FEV1 Divided by Forced Vital Capacity [ Time Frame: From baseline to 2 years ]Percent change from baseline to Month 24.
- Percent Change in DLCO [ Time Frame: From baseline to 2 years ]Percent change from baseline to Month 24.
- Duration of Pulmonary Exacerbations Relative to Treatment Duration [ Time Frame: Over a 2-year period ]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.
- Severity of Pulmonary Exacerbations [ Time Frame: Over a 2-year period ]
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.
Other Outcome Measures:
- Baseline Lung Density at Total Lung Capacity (TLC) and Forced Residual Capacity (FRC) [ Time Frame: Baseline ]
Information from the National Library of Medicine
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years to 65 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
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.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00261833
Locations
| United States, Colorado | |
| Study Site | |
| Denver, Colorado, United States, 80206 | |
| United States, Florida | |
| Study Site | |
| Miami, Florida, United States, 33136 | |
| United States, Pennsylvania | |
| Study Site | |
| Hershey, Pennsylvania, United States, 17033 | |
| United States, Texas | |
| Study Site | |
| Tyler, Texas, United States, 75708 | |
| Australia, New South Wales | |
| Study Site | |
| Darlinghurst, New South Wales, Australia, 2010 | |
| Study Site | |
| New Lambton, New South Wales, Australia, 2305 | |
| Australia, Queensland | |
| Study Site | |
| Brisbane, Queensland, Australia, 4066 | |
| Australia, South Australia | |
| Study Site | |
| Adelaide, South Australia, Australia, 5000 | |
| Australia, Western Australia | |
| Study Site | |
| Nedlands, Western Australia, Australia, 6009 | |
| Australia | |
| Study Site | |
| Fitzroy, Australia, 3065 | |
| Canada, British Columbia | |
| Study Site | |
| Vancouver, British Columbia, Canada, V5Z4E1 | |
| Canada, Nova Scotia | |
| Study Site | |
| Halifax, Nova Scotia, Canada, B3H3A7 | |
| Canada, Ontario | |
| Study Site | |
| Toronto, Ontario, Canada, M5T2S8 | |
| Czech Republic | |
| Study Site | |
| Praha, Czech Republic, 14059 | |
| Denmark | |
| Study Site | |
| Arhus, Denmark, 8000 | |
| Study Site | |
| Hellerup, Denmark, 2900 | |
| Estonia | |
| Study Site | |
| Tartu, Estonia, 51014 | |
| Finland | |
| Study Site | |
| Oulu, Finland, 90220 | |
| Germany | |
| Study Site | |
| Berlin, Germany, 12200 | |
| Study Site | |
| Essen, Germany, 45239 | |
| Study Site | |
| Heidelberg, Germany, 69126 | |
| Study Site | |
| Nürnberg, Germany, 90419 | |
| Ireland | |
| Study Site | |
| Dublin, Ireland, 9 | |
| Poland | |
| Study Site | |
| Krakow, Poland, 31-066 | |
| Study Site | |
| Warsaw, Poland, 01-138 | |
| Romania | |
| Study Site | |
| Bucuresti, Romania, 011026 | |
| Russian Federation | |
| Study Site | |
| Barnaul, Russian Federation | |
| Sweden | |
| Study Site | |
| Malmo, Sweden, 20502 | |
Sponsors and Collaborators
CSL Behring
Investigators
| Study Director: | Senior Director Immonology & Pulmonology, Clinical R&D | CSL Behring |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | CSL Behring |
| ClinicalTrials.gov Identifier: | NCT00261833 |
| Other Study ID Numbers: |
CE1226_4001 1449 ( Other Identifier: CSL Behring ) 2005-003459-12 ( EudraCT Number ) |
| First Posted: | December 5, 2005 Key Record Dates |
| Results First Posted: | January 19, 2015 |
| Last Update Posted: | January 19, 2015 |
| Last Verified: | January 2015 |
Keywords provided by CSL Behring:
|
Alpha1-proteinase inhibitor deficiency Emphysema Chronic augmentation and maintenance therapy |
Additional relevant MeSH terms:
|
Alpha 1-Antitrypsin Deficiency Pulmonary Emphysema Emphysema Pathologic Processes Pulmonary Disease, Chronic Obstructive Lung Diseases, Obstructive Lung Diseases Respiratory Tract Diseases Liver Diseases |
Digestive System Diseases Genetic Diseases, Inborn Subcutaneous Emphysema Protease Inhibitors Alpha 1-Antitrypsin Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Trypsin Inhibitors Serine Proteinase Inhibitors |