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Zemaira in Subjects With Emphysema Due to Alpha1-Proteinase Inhibitor Deficiency

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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:
Information provided by (Responsible Party):
CSL Behring

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

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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


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 :
  1. 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 :
  1. 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.

  2. Percent Change in FEV1 [ Time Frame: From baseline to 2 years ]
    Percent change from baseline to Month 24.

  3. 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.

  4. 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.

  5. 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).

  6. 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.

  7. 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).

  8. Percent Change in Percent Predicted FEV1 [ Time Frame: From baseline to 2 years ]
    Percent change from baseline to Month 24.

  9. Percent Change in FEV1 Divided by Forced Vital Capacity [ Time Frame: From baseline to 2 years ]
    Percent change from baseline to Month 24.

  10. Percent Change in DLCO [ Time Frame: From baseline to 2 years ]
    Percent change from baseline to Month 24.

  11. 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.

  12. 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:
  1. Baseline Lung Density at Total Lung Capacity (TLC) and Forced Residual Capacity (FRC) [ Time Frame: Baseline ]


Information from the National Library of Medicine

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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
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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
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Study Director: Senior Director Immonology & Pulmonology, Clinical R&D CSL Behring
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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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:
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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