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

This study has been completed.
Information provided by (Responsible Party):
CSL Behring Identifier:
First received: December 2, 2005
Last updated: October 6, 2013
Last verified: October 2013

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 Intervention Phase
Alpha1-proteinase Inhibitor Deficiency
Biological: Alpha1-proteinase inhibitor
Other: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:

Further study details as provided by CSL Behring:

Primary Outcome Measures:
  • Annual rate of change in lung density [ Time Frame: Over a 2-year period ] [ Designated as safety issue: No ]
    As measured by CT lung densitometry

Secondary Outcome Measures:
  • Annual rate of pulmonary exacerbations [ Time Frame: Over a 2-year period ] [ Designated as safety issue: No ]
  • Change in forced expiratory volume in 1 second (FEV1) [ Time Frame: From baseline to 2 years ] [ Designated as safety issue: No ]
  • Time to first pulmonary exacerbation [ Time Frame: Over a 2-year period ] [ Designated as safety issue: No ]
  • Change in lung density [ Time Frame: From baseline to 2 years ] [ Designated as safety issue: No ]
    As measured by CT lung densitometry

  • Change in exercise capacity [ Time Frame: From baseline to 2 years ] [ Designated as safety issue: No ]
    As measured using the incremental shuttle walk test.

  • Change in patient-reported symptoms [ Time Frame: From baseline to 2 years ] [ Designated as safety issue: No ]
    As measured by the symptoms score component of the St George's Respiratory Questionnaire

  • Frequency and intensity of adverse events (AEs) [ Time Frame: Over a 2-year period ] [ Designated as safety issue: Yes ]
    Number of subjects with at least one AE, and the number of subjects with mild, moderate or severe AEs. The AE intensity is defined as mild (does not interfere with routine activities), moderate (interferes with routine activities) and severe (impossible to perform routine activities).

  • Change in FEV1 as a percentage of predicted [ Time Frame: From baseline to 2 years ] [ Designated as safety issue: No ]
  • Change in FEV1 divided by forced vital capacity [ Time Frame: From baseline to 2 years ] [ Designated as safety issue: No ]
  • Change in diffusion capacity for carbon monoxide [ Time Frame: From baseline to 2 years ] [ Designated as safety issue: No ]
  • Characteristics of pulmonary exacerbations - proportion of treatment duration [ Time Frame: Over a 2-year period ] [ Designated as safety issue: No ]

    Proportion of total treatment duration spent:

    • experiencing exacerbations
    • on antibiotic treatment for exacerbations
    • hospitalized for exacerbations

  • Characteristics of pulmonary exacerbations - number of subjects [ Time Frame: Over a 2-year period ] [ Designated as safety issue: No ]

    Number of subjects:

    • requiring antibiotic treatment for exacerbations
    • hospitalized for exacerbations

Enrollment: 180
Study Start Date: March 2006
Study Completion Date: September 2012
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Zemaira® Biological: Alpha1-proteinase inhibitor
60 mg/kg b.w. i.v. weekly
Other Name: Zemaira®
Placebo Comparator: Placebo Other: Placebo
Lyophilized preparation / 60 mg/kg body weight / weekly


Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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 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 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.
  Contacts and Locations
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Please refer to this study by its identifier: NCT00261833

  Show 28 Study Locations
Sponsors and Collaborators
CSL Behring
Study Director: Senior Director Immonology & Pulmonology, Clinical R&D CSL Behring
  More Information

Additional Information:
No publications provided

Responsible Party: CSL Behring Identifier: NCT00261833     History of Changes
Other Study ID Numbers: CE1226_4001, 1449, 2005-003459-12
Study First Received: December 2, 2005
Last Updated: October 6, 2013
Health Authority: United States: Food and Drug Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration
Canada: Ethics Review Committee
Canada: Health Canada
Czech Republic: Ethics Committee
Czech Republic: State Institute for Drug Control
Denmark: Danish Medicines Agency
Denmark: Ethics Committee
Denmark: The Danish National Committee on Biomedical Research Ethics
Estonia: The State Agency of Medicine
Finland: Ethics Committee
Finland: Finnish Medicines Agency
Germany: Ethics Commission
Germany: Paul-Ehrlich-Institut
Ireland: Irish Medicines Board
Ireland: Medical Ethics Research Committee
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Romania: National Medicines Agency
Sweden: Medical Products Agency

Keywords provided by CSL Behring:
Alpha1-proteinase inhibitor deficiency
Chronic augmentation and maintenance therapy

Additional relevant MeSH terms:
Alpha 1-Antitrypsin Deficiency
Alpha 1-Antitrypsin
Pulmonary Emphysema
Digestive System Diseases
Genetic Diseases, Inborn
Liver Diseases
Lung Diseases
Lung Diseases, Obstructive
Pathologic Processes
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Diseases
Subcutaneous Emphysema
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Serine Proteinase Inhibitors
Trypsin Inhibitors processed this record on November 24, 2014