Extension Study of Zemaira® i.v. Administration in Subjects With Emphysema Due to alpha1-proteinase Inhibitor Deficiency.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
CSL Behring
ClinicalTrials.gov Identifier:
NCT00670007
First received: April 29, 2008
Last updated: July 13, 2016
Last verified: July 2016
  Purpose
This study is a continuation of the placebo-controlled study CE1226_4001 (NCT00261833) to evaluate the efficacy and safety of Zemaira® intravenous (i.v). administration in subjects with emphysema due to alpha1-proteinase inhibitor deficiency. The long-term verification of a disease-modifying benefit of Zemaira® on the progression of emphysema will be assessed by volume-adjusted lung density, measured yearly by computed tomography (CT).

Condition Intervention Phase
Emphysema
Alpha 1-proteinase Inhibitor Deficiency
Biological: Alpha1- proteinase inhibitor [human]
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label, Non-controlled, Multicenter, Multinational Study to Evaluate the Efficacy and Safety of Zemaira® Administration in Chronic Augmentation and Maintenance Therapy in Subjects With Emphysema Due to alpha1-proteinase Inhibitor Deficiency Who Completed Clinical Study CE1226_4001

Resource links provided by NLM:


Further study details as provided by CSL Behring:

Primary Outcome Measures:
  • Rate of Change of Adjusted Lung Density [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    As measured by centralized, standardized computer tomographic (CT) lung densitometry. CT scans were acquired at 2 inspiration states: TLC (Total Lung Capacity; ie, full inspiration) and FRC (Functional Residual Capacity; ie, full expiration). Results were adjusted for total lung volume and are presented as point estimates for the average rate of decline in the early start and delayed start subgroups from a linear random regression model with country, inspiration state (only for 'TLC and FRC state'), time (time elapsed since Day 1 [CE1226_4001]), treatment and treatment by time interaction as fixed effects and subject and subject by time interaction as random coefficients.


Secondary Outcome Measures:
  • Absolute Change in Adjusted Lung Density [ Time Frame: From baseline to 2 years ] [ Designated as safety issue: No ]
    Absolute change from baseline to 2 years 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 and are presented as point estimates for the average absolute change in the early start and delayed start subgroups from an analysis of covariance (ANCOVA) model with country, treatment, and baseline lung density as fixed effects and inspiration state as a repeated random effect. The baseline is the last assessment from the preceding study CE1226_4001.

  • Percent Change in Adjusted Lung Density [ Time Frame: From baseline to 2 years ] [ Designated as safety issue: No ]
    Percent change from baseline to 2 years 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 and are presented as point estimates for the average percent change in the early start and delayed start subgroups from an analysis of covariance (ANCOVA) model with country, treatment, and baseline lung density as fixed effects and inspiration state as a repeated random effect. The baseline is the last assessment from the preceding study CE1226_4001.

  • Change in Subject-reported Symptoms [ Time Frame: From baseline to 2 years ] [ Designated as safety issue: No ]
    Patient-reported symptoms were measured using the St George's Respiratory Questionnaire (SGRQ). SGRQ total, symptoms, activity and impact scores range from 0 to 100, with higher scores indicating more limitations, and change from baseline below zero (0) is favorable, indicating improvement.

  • Percent Change in Lung Function as Measured by Forced Expiratory Volume in 1 Second (FEV1) [ Time Frame: From baseline up to 2 years ] [ Designated as safety issue: No ]
  • Percent Change in Lung Function as Measured by Ratio of FEV1/FVC (Forced Vital Capacity) [ Time Frame: From baseline up to 2 years ] [ Designated as safety issue: No ]
  • Percent Change in Lung Function as Measured by Percent Predicted FEV1 [ Time Frame: From baseline up to 2 years ] [ Designated as safety issue: No ]
  • Number of Subjects With Pulmonary Exacerbations [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Annual Rate in Subject Years of Pulmonary Exacerbations [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Annual exposure‑adjusted incidence rate of pulmonary exacerbations.

  • Time to First Pulmonary Exacerbation [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Percentage of Subjects With Treatment Emergent Adverse Events [ Time Frame: From baseline up to 2.5 years ] [ Designated as safety issue: Yes ]
    Percentage of subjects with treatment-emergent adverse events (TEAEs): overall, by severity, by relatedness, by seriousness, and which occurred within 24 hours of Zemaira administration.


Enrollment: 140
Study Start Date: April 2008
Study Completion Date: September 2014
Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Zemaira® Biological: Alpha1- proteinase inhibitor [human]
Lyophilized preparation of 60 mg/kg body weight intravenously once per week
Other Names:
  • Zemaira®
  • Respreeza®

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects who have completed the 2-year treatment and observation period in the Phase 3/4 Zemaira® CE1226_4001 study (NCT00261833) and are willing to sign informed consent
  • Males, and non-pregnant, non-lactating females, whose screening pregnancy test is negative and who are using contraceptive methods deemed reliable by the investigator

Exclusion Criteria:

  • Individuals residing in the US
  • Current evidence of alcohol abuse or abuse of 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
  • Current tobacco smoker (smoking must be discontinued for at least 6 months prior to study participation)
  • 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
  • Inability to perform necessary study procedures
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00670007

  Show 21 Study Locations
Sponsors and Collaborators
CSL Behring
Investigators
Study Director: Program Director, Clinical R&D CSL Behring
  More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: CSL Behring
ClinicalTrials.gov Identifier: NCT00670007     History of Changes
Other Study ID Numbers: CE1226_3001  1466  2007-007129-38 
Study First Received: April 29, 2008
Results First Received: June 2, 2016
Last Updated: July 13, 2016
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Canada: Ethics Review Committee
Ireland: Irish Medicines Board
Ireland: Medical Ethics Research Committee
Finland: Ethics Committee
Australia: Department of Health and Ageing Therapeutic Goods Administration
Finland: Finnish Medicines Agency
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Germany: Paul-Ehrlich-Institut
Czech Republic: Ethics Committee
Czech Republic: State Institute for Drug Control
Denmark: Danish Medicines Agency
Estonia: The State Agency of Medicine
Romania: National Medicines Agency
Sweden: Medical Products Agency

Keywords provided by CSL Behring:
Alpha1-proteinase inhibitor deficiency
Chronic augmentation and maintenance therapy
Emphysema
Emphysema due to Alpha 1-proteinase inhibitor deficiency

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

ClinicalTrials.gov processed this record on August 25, 2016