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

Study Overview
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Brief Summary
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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).

Official Title
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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

Conditions
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Emphysema, Alpha 1-proteinase Inhibitor Deficiency

Intervention / Treatment
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* Biological: Alpha1- proteinase inhibitor [human]


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Zemaira®<br> | Biological: Alpha1- proteinase inhibitor [human]<br>* Lyophilized preparation of 60 mg/kg body weight intravenously once per week<br>* Other names: Respreeza®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Change of Adjusted Lung Density | 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. | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change in Adjusted Lung Density | 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. | From baseline to 2 years | 
| Percent Change in Adjusted Lung Density | 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. | From baseline to 2 years | 
| Change in Subject-reported Symptoms | 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. | From baseline to 2 years | 
| Percent Change in Lung Function as Measured by Forced Expiratory Volume in 1 Second (FEV1) |  | From baseline up to 2 years | 
| 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 | 
| Number of Subjects With Pulmonary Exacerbations |  | Up to 2 years | 
| Annual Rate in Subject Years of Pulmonary Exacerbations | Annual exposure-adjusted incidence rate of pulmonary exacerbations. | Up to 2 years | 
| Time to First Pulmonary Exacerbation |  | Up to 2 years | 
| Percentage of Subjects With Treatment Emergent Adverse Events | 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. | From baseline up to 2.5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alpha1-proteinase inhibitor deficiency, Chronic augmentation and maintenance therapy, Emphysema, Emphysema due to Alpha 1-proteinase inhibitor deficiency