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

Phase 4

Completed

• Conditions: Alpha 1-proteinase Inhibitor Deficiency; Emphysema
• Interventions: Biological: Alpha1- proteinase inhibitor [human]

• Registration Number: NCT00670007
• Lead Sponsor: CSL Behring

Brief Summary

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).

Detailed Description

Not available

Study Timeline

• Study Start: 2008-04
• Study First Submitted: 2008-04-29
• Study First Submitted QC: 2008-04-30
• Study First Posted: 2008-05-01
• Primary Completion: 2014-09
• Study Completion: 2014-09
• Disposition First Submitted: 2015-09-02
• Disposition First Submitted QC: 2015-09-02
• Disposition First Posted: 2015-09-18
• Results First Submitted: 2016-06-02
• Results First Submitted QC: 2016-06-02
• Status Verified: 2016-07
• Results First Posted: 2016-07-12
• Last Update Submitted: 2016-07-13
• Last Update Posted: 2016-08-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 140

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Zemaira®	Alpha1- proteinase inhibitor [human]	-

Primary Outcome Measures

Name	Time	Method
Rate of Change of Adjusted Lung Density	Up to 2 years	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

Name	Time	Method
Time to First Pulmonary Exacerbation	Up to 2 years
Percent Change in Adjusted Lung Density	From baseline to 2 years	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	From baseline to 2 years	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.
Absolute Change in Adjusted Lung Density	From baseline to 2 years	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 Lung Function as Measured by Forced Expiratory Volume in 1 Second (FEV1)	From baseline up to 2 years
Number of Subjects With Pulmonary Exacerbations	Up to 2 years
Percentage of Subjects With Treatment Emergent Adverse Events	From baseline up to 2.5 years	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.
Percent Change in Lung Function as Measured by Ratio of FEV1/FVC (Forced Vital Capacity)	From baseline up to 2 years
Percent Change in Lung Function as Measured by Percent Predicted FEV1	From baseline up to 2 years
Annual Rate in Subject Years of Pulmonary Exacerbations	Up to 2 years	Annual exposure-adjusted incidence rate of pulmonary exacerbations.

Trial Locations

Locations (1)

Study Site; 🇸🇪 Malmo, Sweden